Keywords

The following keywords are recognised, where *n*, *x* and *exec* are integer,
real and character data, respectively.

*2D*: restrict the system to the*x*-*y*plane.*AAORIENT k sigma*: adds a mean field to the general angle-axis potential. The strength of the field is determined by the parameter*k*(default 1). Positive*k*values will tend to align the reference frames of all the rigid bodies, while negative*k*values penalise alignment. The field is designed to fix geometry optimisation problems caused by rigid body rotations that give very small Hessian eigenvalues. The zero eigenvalues should be shifted roughly in proportion to*k*. If*range*is specified, the field is modulated by a Gaussian with standard deviation*range*, to allow local alignment while removing the contributions from distant rigid bodies.*ACE n*: for use with CHARMM runs that employ the ACE implicit solvent model.*n*specifies the number of calls to the CHARMM energy and gradient for which lists are held fixed. The default value of*n*is 50. Note:*ENDNUMHESS*must be used with the ACE solvent model. Otherwise`OPTIM`will attempt to use incorrect second derivatives.*ENDNUMHESS*will be needed in the`odata.start`,`odata.finish`and`odata.connect`files. For`odata.start`and`odata.finish`the keyword*ENDHESS*must also be included.*ACKLAND id*: specifies an Ackland embedded atom metal potential coded by Dr Mihai-Cosmin Marinica.*id*specifies the particular metal: 5 is iron, 6 is a different iron, 7 is tungsten. Positive values for*id*specify periodic boundary conditions, where box lengths must be specified by the*PERIODIC*keyword. See also*ACKLAND1*and*ACKLAND2*.*ACKLAND1*: specifies the original Ackland embedded atom metal potential coded by Dr Mihai-Cosmin Marinica. The*ACKLAND*keyword is also needed.*ACKLAND2*: specifies the new Ackland embedded atom metal potential coded by Dr Mihai-Cosmin Marinica. The*ACKLAND*keyword is also needed.*ADJUSTK frq tol frac*: causes the force constant to be adjusted dynamically in doubly-nudged elastic band runs.*frq*is the frequency at which the adjustment is made, based on the deviation of the image spacing from uniformity. If the spacing deviates by more than*tol*then the force constant is increased by*frac*; if it is lower then the force constant is decreased by*frac*.*ADM n*: will cause the interatomic distance matrix to be printed every*n*cycles; the default for*n*is 20. This matrix is not printed by default.*ALIGNRBS n1, n2, ...*: For use with*GENRIGID*. Specify that the translation and rotation used for endpoint alignment should be calculated from a subset of rigid bodies in the system, specified by*n1, n2, ...*. The number of arguments that may be specified is limited by the allowed length of the keyword line. The calculated translation and rotation are applied to the whole system. Note, there is currently no permutational alignment implemented, so this routine will not detect permutational isomers.*ALPHA*: sets exponent value for averaged Gaussian and Morse potentials, default value is 6.*ALLPOINTS*: turns on printing of coordinates to file`points`for all intermediate configurations. Default is false.*AMBER12 inpcrd inpcrdformat*: specifies calculation with the interfaced version of the AMBER 12`pmemd`program. AMBER 12 requires an additional input file,`min.in`, which specifies keywords for the AMBER 12 potential. It also requires appropriate topology and coordinates, in files named`coords.prmtop`and`coords.inpcrd`respectively. For details, see the AMBER 12 manual. As with the AMBER 9 interface, cutoffs are smoothed, using the`min.in`keyword`ifswitch=1`. Additional keywords are as AMBER 9, though it should be noted that analytical second derivatives are not available through use of the*NAB*keyword. Users of`GMIN`should note that, unlike in`GMIN`, specifying*AMBER12*without*inpcrdformat*assumes that input coordinates are provided in xyz, rather than AMBER restart format.*A12DECOMPE*: dumps out decomposed energy contribution at the end of optimisations.*A12DECOMPEALL*dumps the decomposition for every call to potential.*AMBER9 inpcrd inpcrdformat*: specifies a calculation with the interfaced version of the Amber 9 program package. From this package the Amber force fields are being used, with small modifications (*e.g.*smooth cut-offs). Starting coordinates do not need to be specified in the`odata`file, they are read from*inpcrd*instead (default*coords.inpcrd*), in Amber inpcrd file format specified by the second optional argument*inpcrdformat*. If the second argument is missing, it is assumed that*inpcrd*contains only three columns with the xyz coordinates of all atoms, in the same order as in the topology file. To start a run with this interface, several auxiliary files are required in the same directory: input coordinate file*coords.inpcrd*, parameter topology file*coords.prmtop*, input file to Amber containing force field specifications*min.in*, and, if desired, a coordinate file different from*coords.inpcrd*containing starting coordinates. To turn on smooth cutoffs for the Generalised Born force fields, the keyword*ifswitch=1*has to be used in the*&cntrl*namelist block of*min.in*. When using the*AMBER9*keyword, any calculated second derivatives will be numerical. If one wants analytical second derivatives, the*NAB*keyword should be used instead, with the same syntax. The NAB interface does not currently support smooth cutoffs, so analytical second derivatives are only recommended for stationary points calculated with large cutoffs. Additional keywords for the AMBER 9 runs are*NAB*and*DUMPSTRUCTURES*.*AMBERIC*: interpolation in bhinterp with internal coordinates. If BACKBONE specified additionally (AMBERIC BACKBONE) the protein backbone is also interpolated in internals. Does not work for polymers.*AMBERSTEP*: perturbation/twisting in bhinterp done with internal coordinates*AMBPERTONLY n*:only perturb angles for which the difference between the start and end configuration before the interpolation was greater than n (i.e. n= 30.0 - 30 degree). Probability of perturbation depends on this likelihood (and on position in chain)*AMBPERTOLD*: use original perturbation scheme. Now angles depend on position in chain - larger perturbation if at the end.*ANGLEAXIS*: specifies angle/axis coordinates for rigid body TIP potentials.*ARCTOL tol*: specifies the accuracy tolerance for computing the inverse arc length used in the cubic spline interpolated string methods for double-ended transition state searches. The default is 10^{-4}.*ATOMMATCHDIST*: used for bulk systems, providing an alternative method for finding the shortest distance between structures. This method is particularly useful for finding the shortest distance between very similar structures such as defective crystal structures. The method is an extension of the original bulkmindist.f90 routine for matching permutationl isomers. Atoms are overlayed and the number of exactly matching g atoms is maximised. (ATOMMATCHINIT uses atom matching only for aligning initial structures and then reverts to the default distance method.) With ATOMMATCHDIST/INIT, the method is non-deterministic to maximise efficiency. It has been optimised to work particularly well for providing small distan ces between similar structures and for removing very large distances. However, it will not always outperform the default method for middling distances. Currently only one method for calculating distances, atom matching or the default, can be used.*ATOMMATCHFULL*: As for*ATOMMATCHDIST*, but provides a slow deterministic result that should always outperform or equal the default distance calculation and ATOMMATCHDIST but may never finish.*ATOMMATCHINIT*: see*ATOMMATCHDIST*.*AUCMLPLOG*: Logical, if included, a log function is used as loss function instead of AUC. This keyword makes the AUCMLPVB3 routine equivalent to the original MLPVB3 routine. Default is*FALSE*.*AUCMLPVB3 in hidden out data*: Specifies a single-layered neural network as with keyword*λ**β**MLPVB3*(see below), with*in*input nodes,*hidden*hidden nodes,*out*output nodes and*λ*as the L2 regularisation parameter.*data*is the number of data points the model trains with, stored in a file called*MLPData*. This file should be formatted as follows:*y*^{1}*x*_{1}^{1}*x*_{2}^{1}*x*_{3}^{1}... *y*^{2}*x*_{1}^{2}*x*_{2}^{2}*x*_{3}^{2}... *y*^{3}*x*_{1}^{3}*x*_{2}^{3}*x*_{3}^{3}... ... *y*^{Ndata}*x*_{1}^{Ndata}*x*_{2}^{Ndata}*x*_{3}^{Ndata}... *y*^{i}is the outcome for data point*i*, and*x*_{j}^{i}is the*j*th input feature for data point*i*. The features will be read starting from the feature in column*start*(ignoring the*y*column).Unlike MLPVB3, instead of calculating the associated loss value, an approximated AUC is calculated. The true AUC value is given by the following non-differentiable function:

*AUC*(;) =*Θ**p*_{1}(;) -*p*_{1}(;),(1) *Θ*(*x*) is the Heaviside step function (1 for*x*> 0 and 0 otherwise). This function is not differentiable, so we must use an approximate function. The function to be minimised is*E*(;) = .(2) *p*_{1}(;) is the softmax probability of the neural network giving output class 1 for data point*i*, given weights . The sums are over data points where the true class is 1, of which there are*N*_{p}, and over data points where the true class is not 1, of which there are*N*_{n}.*β*is the parameter for the sigmoid function*σ*(*z*) .(3) *β*make curve steeper, hence approximate the true AUC more closely. The maximum value allowed for*β*is set at 500 to prevent floating-point underflow errors. If*β*is set higher than this value, the maximum value of 500 will override it and be used instead.*AVOIDCOLLISIONS tol*: For use with*GENRIGID*. When performing the angle-axis interpolation prior to a DNEB run, check the energy of the highest-energy image. If it is greater than*tol*, then for each rigid body in turn we reverse the sense of interpolation for its angle axis vector (so the body rotates in the opposite direction to before). Hopefully this will avoid two rigid bodies colliding (which is assumed to be what causes the high-energy image). If reversing the rotation direction results in a decreased maximum image energy, the new sense of rotation is accepted. If at any point the maximum image energy falls below*tol*, the testing process is stopped.This is currently a rather crude method and not terrible effective. It will be improved in the future.

*AXIS n*: specifies the highest symmetry axis to search for in routine**symmetry**; default is six.*BBCART*: use Cartesian coordinates for all backbone atoms and for prolines. Right now, only works for natural internals.*BBRSDM gamma epsilon sigma1 sigma2 M alpha gmax nstep*: specifies the steepest-descent minimiser introduced by Barzilai and Borwein [12] and modified by Raydan [13] for a maximum of*nstep*iterations in a pathway calculation. The method uses gradient only information with the convergence criterion*gmax*for the RMS force and does not guarantee descent in the objective function in each iteration. The input parameters include an integer*M*≥ 0,*γ*∈(0, 1), 0 <*σ*_{1}<*σ*_{2}< 1, and an initial value for*α*. Raydan reported with*γ*= 10^{-4},*ε*= 10^{-10},*σ*_{1}= 0.1,*σ*_{2}= 0.5,*α*_{0}= 1.0, and*M*= 10.*BFGSCONV gmax*:*gmax*is the convergence criterion for the root-mean-square gradient, default 0.001. This is also the convergence criterion for the subspace minimisations in hybrid EF/BFGS transition state searches, for use with*BFGSTS*.*BFGSMIN gmax*: instructs the program to perform an LBFGS minimisation.*gmax*is the convergence criterion for the root-mean-square gradient, default 0.001.*BFGSSTEP*: instructs the program to step off a saddle point along the eigenvector corresponding to the smallest negative eigenvalue without diagonalizing the Hessian to find this eigenvector. It is possible to step off parallel and antiparallel to this eigenvector by specifying positive or negative values for the*MODE*parameter.*BFGSTS*need not be set, but see also*PATH*and*CONNECT*. After taking the first step the program switches to energy minimisation using whichever algorithm is specified, e.g.*BFGSMIN*,*SEARCH 0*,*SEARCH 6*,*RKMIN*,*BSMIN*, etc. It should no longer be necessary to use this keyword, as OPTIM will now perform a pathway calculation after a single-ended transition state search if the*PATH*keyword is present. The minimiser for the pathway phase can be chosen independently of the transition state search algorithm by specifying one of the*BFGSMIN*,*BSMIN*,*RKMIN*,*BBRSDM*, or*PMPATH*keywords.*BFGSSTEPS n*: sets the maximum number of steps allowed in LBFGS minimisations. Default value is the value of the*STEPS*parameter. However, for*NEWNEB*this parameter is specified via the*NEWCONNECT*or*NEWNEB*line.*BFGSTS nevs ncgmax1 ncgmax2 ceig nevl*: instructs the program to perform a hybrid BFGS/eigenvector-following transition state search.*nevs*is an integer that defines the largest number of iterations allowed in the calculation of the smallest Hessian eigenvalue; default 500.*ncgmax1*is an integer that defines the largest number of BFGS steps allowed in the subspace minimisation before the eigenvalue is deemed to have converged; default 10.*ncgmax2*is an integer that defines the largest number of BFGS steps allowed in the subspace minimisation after the eigenvalue is deemed to have converged; default 100. This parameter is ignored if*NOIT*is set. The eigenvalue is deemed to be converged if the modulus of the overlap between the corresponding eigenvector and that saved from the previous step exceeds 0.999 and we have the right number of negative eigenvalues.*ceig*is a double precision parameter that sets the convergence criterion for the calculation of the smallest non-zero Hessian eigenvalue. If*NOHESS*is set*ceig*is compared to the RMS `force' corresponding to the Rayleigh-Ritz expectation value that is minimised to get the smallest eigenvalue. If the Hessian is used via iteration or*NOIT*then*ceig*is compared to the percentage change in the eigenvalue between successive steps. The default value is 1.0, which is more appropriate to the latter case. Smaller values are probably necessary in BFGS/BFGS calculations.*nevl*is an integer that defines the largest number of iterations allowed in the calculation of the largest Hessian eigenvalue; default 100. Not needed if*NOHESS*of*NOIT*is set.*BFGSTSTOL tol*: tolerance for eigenvector overlap in BFGSTS where the number of tangent space steps switches from small to large. If the overlap differs from unity by less than*tol*then the larger number of steps is used in the tangent space minimisation. 0.0001 is the default value.*BFGSTSPC evpc*: convergence condition for absolute value of percentage change in the Hessian eigenvalue calculated using the Rayleigh-Ritz procedure for transition state searches with no Hessian. Default value is 50%. This condition complements the tolerance parameter*ceig*of*BFGSTS*above. It can prevent premature convergence when an eigenvalue estimate passes through zero, where the RMS `force' can be small and accidentally satisfy the condition on*ceig*.*BFGS*: specifies that the full BFGS minimiser should be used. Inefficient compared to LBFGS.*BGUPTAT NTYPEA AAA PAA QAA ZAA R0AA*: One of the required keywords to specify a Binary Gupta run. NTYPEA is specified, followed by the potential parameters for the A-A interactions. See also BGUPTATAB and BGUPTATBB. The atom coordinates in odata must also be labelled by G1 and G2 (representing A and B type atoms respectively). All the G1 atoms must be first in the file, followed by the G2 atoms (the calculation is performed assuming the coordinates are of NTYPEA A atoms first, and the coordinates listed afterwards are B).*BGUPTATAB AAB PAB QAB ZAB R0AB*: The line to specify the potential parameters for the A-B interactions for a Binary Gupta run.*BGUPTATBB ABB PBB QBB ZBB R0BB*: Specifies the B-B interaction parameters.*BHDEBUG*: printing localised debugging output for*BHINTERP**BHINTERP dthresh maxe bhsteps conv T stepsize accrat K sfrac ICINTERP*: interpolation between minima in double-ended searches using*CONNECT*is changed to search for likely intermediate minima. The interpolation is performed for pairs of minima separated by a minimum distance more than*dthresh*. Intermediate minima are only accepted if their energy is below*maxe*. A basin-hopping global optimisation run of*bhsteps*is run for each pair of end point minima within*dthresh*using an RMS gradient convergence criterion of*conv*, a temperature parameter of*T*, and a maximum step size for perturbations of*stepsize*. The step size is adjusted dynamically towards an acceptance ratio target of*accrat*. The objective function consists of the energy of the minimum on the potential energy surface plus the energy corresponding to harmonic springs of force constant*K*stretched to displacements corresponding to the minimum distance between the new minimum and the end points.*sfrac*is used in the initial interpolation: a value of 0.5 will put the initial guess half-way between the end points, and in general the geometry will be*sfrac*times one end point plus (1 -*sfrac*) times the other. For large distances, using a value other than a half may be helpful. If*ICINTERP*is present then amino acid side chains are interpolated using internal coordinates for CHARMM runs. The step size is interpreted in degrees for CHARMM, where the perturbations used to step between minima are performed using dihedral angle twists. The algorithm is applied recursively between minima as new minima are found. A new minimum will not be accepted if both distances to the minima we are currently trying to interpolate between are greater than the minimum distance between these minima.*BHINTERPUSELOWEST CHECKENER bhstepsmin*: take the minimum with the lowest potential energy as the best intervening structure, rather than the one with the lowest potential energy plus spring energy. The accept/reject procedure in the*BHINTERP*procedure is still based on the potential energy plus spring energy. CHECKENER is an optional argument. If it is set, for each accepted BHSTEP it is checked whether the potential energy of the best intervening structure is smaller than*maxe*, which is determined together with the*BHINTERP*keyword. If so, and if at least*bhstepsmin*BHINTERP steps have been executed, the BHINTERP run for the current pair of endpoints is stopped. This procedure ensures some dynamic adjustment of BHINTERP to the distance between the two endpoints in question. If CHECKENER is not given,*BHINTERP*performs*bhsteps*steps (see above).*bhstepsmin*is an optional argument, whose default is 1.*BINARY ntypea epsab epsbb sigmaab sigmabb*: specifies a binary Lennard-Jones system for use with the LP or LS atom types.*ntypea*is the number of type A atoms—the rest are assumed to be type B and appear at the end of the list of coordinates.*ε*_{AA}=*σ*_{AA}= 1 define the units of energy and length, and*epsab*=*ε*_{AB},*epsbb*=*ε*_{BB},*sigmaab*=*σ*_{AB},*sigmabb*=*σ*_{BB}.*BISECT dthresh maxe bisectsteps attempts ICINTERP*: specifies the*BISECT*interpolation option, where no transition state searches are run. This option is intended for use with*DUMMYTS*in PATHSAMPLE. The distance threshold parameter specifies that bisection between consecutive minima should occur if their minimum distance is greater than*dthresh*. The interpolated geometry is minimised and compared with the starting structures. New minima are only accepted if their energy is below*maxe*; they are added to the current list of known minima between the two starting structures originally supplied to OPTIM.*bisectsteps*is the maximum number of bisection steps, and*attempts*is the number of attempts per step for a given pair. If minimisation leads to one of the end points the interpolation is changed to use fractions of the two structures that become increasingly skewed, as for the adjustment of*sfrac*with*BHINTERP*, above. If*ICINTERP*is present then amino acid side chains are interpolated using internal coordinates for CHARMM runs.*BLN rkr rkt*: general BLN protein bead model.[21,22]*rkr*and*rkt*are the spring constants for bond length and bond angle terms. An auxiliary file`BLNsequence`is required to specify all the other parameters and the sequence, along with a code to define the secondary structure template that changes some of the parameters. For example, the format of`BLNsequence`for protein L is: comment: LJREP_BLN >0 and LJATT_BLN <0 for B-B, L-L and L-B, N-L and N-B and N-N 1.0D0 -1.0D0 0.33333333333333D0 0.33333333333333D0 1.0D0 0.0D0 comment: coefficients A, B, C, D of 1 + cos*φ*, 1 - cos*φ*, 1 + cos 3*φ*and 1 + cos(*φ*+*π*/4) comment: for Helical, Extended and Turn residues in order, four per line 0.0D0 1.2D0 1.2D0 1.2D0 0.9D0 0.0D0 1.2D0 0.0D0 0.0D0 0.0D0 0.2D0 0.0D0 LBLBLBLBBNNNBBBLBLBBBNNNLLBLLBBLLBNBLBLBLBLNNNLBBLBLBBBL EEEEEETEHTHEEEEEEEEHHEHHHHHHHHHHEHTEEEEEEETTTEEEEEEEE*BLNGO*: specifies a Gō potential with the same form as the*k*_{r}*k*_{θ}*λ**BLN*potential. The parameters*k*_{r}and*k*_{θ}are the same as those used for the*BLN*keyword and a`BLNsequence`file is required. Also needed is an auxiliary file,`contactmap`, containing the pairs of residues in contact in the native state of the protein with one pair of residue numbers in each line of the file. An optional parameter,*λ*, specifies the strength of the non-native interactions in a scaled*BLN*potential [23].*BOND a1 a2*: Specifies an extra bond to add to the structure when using internal coordinates. Adding a bond between ligand and protein allows the generation of a complete set of natural internal coordinates. The bond should be between two atoms numbered relatively close together to avoid KD getting too large. The recommended method of dealing with a ligand is still to use Cartesian coordinates for it with*CARTRESSTART*instead.*BOWMAN n path*: specifies one of the Bowman potentials for water.*n*is 2 or 3, where 2 is the full Bowman potential and 3 is the so-called Kumar-Skinner 3-body expansion, which is faster, but less accurate.*path*is the location of the various data files coef-3b/&sstarf#star; called by the potential. The file`h4o2.pes4.coeff.dat`must be present in the current working directory, and the atom order must be H1a, H1b, H2a, H2b,..., O1, O2,... The energy is in hartree and the distance is in Angstrom.*BSMIN gmax eps*: calculates a steepest-descent path using gradient only information with convergence criterion*gmax*for the RMS force and initial precision*eps*. The Bulirsch-Stoer algorithm is used.*BULK boxx boxy boxz*: specifies that a periodically repeated supercell is being used. The parameters boxx, boxy, and boxz specify the dimenions of the rectangular box. Note that many potentials specify box dimensions using the PARAMS keyword. When using*RIGIDINIT*, specify box dimensions using*BULK*as well as with*PARAMS*.*CADPAC system exec*: tells the program to read derivative information in CADPAC format.*system*is a string to identify the system and*exec*is the name of an executable that will generate a CADPAC input deck from a points file. If*exec*is omitted its name is assumed to be*editit.system*.*CALCDIHE*: calculates an order parameter for CHARMM and UNRES with respect to a reference structure in file`ref.crd`.*CALCRATES temp h*: rate constants will be calculated for each transition state found in a*CONNECT*or*PATH*run, or using saved information in an old`path.info`file if*READPATH*is specified. Both forward and backward canonical rate constants are calculated from transition state theory at temperature*temp*(default*temp*=1), and values are given for both quantum and classical harmonic vibrational partition functions.*h*is the value of Planck's constant in suitable reduced units for the corresponding potential (default value 1).*CAMSHIFT csversion svnroot shiftfile csn csalpha*: uses chemical shifts as restraints during the optimization procedure. Currently,*CAMSHIFT*can only be used together with*CHARMM*.*csversion*is a string that specifies the method for combining the two potentials: MERGE means (1 -*α*)**Charmm*+*α***Camshift*, ORIGINAL means*Charmm*+*α***Camshift*, and NOFF means*α***Camshift*.*svnroot*specifies the svn root directory (e.g., $HOME/svn/).*shiftfile*is the file containing the experimental shifts, which has to be located in the working directory.*csversion*,*svnroot*and*shiftfile*all have to be specified together with*CAMSHIFT*.*csn*and*csalpha*are optional parameters. They define the tolerance parameter of the CamShift energy profile, and the relation between CamShift and the force field, respectively. Default values for both are 1.0.*CANDIDATES value*: specifies which images in an NEB interpolation should be used as starting points for transition state searches.*value*can be `high' (just the highest image) or `maxim' (all local maxima, the default).*CAPSID rho eps r h*: specifies a potential for rigid pentagonal pyramids with Morse parameter*rho*, repulsive strength*eps*, radius*r*, and height*h*(in units of*r*).*h*may be omitted, in which case it defaults to 0.5.*CARTRESSTART n*: When using internal coordinates, specifies that Cartesian coordinates are to be used for all residues starting with the*n*^{th}. Useful for molecules with a non-peptide ligand at the end of the structure. Warning!: if any of the residues numbered n or above are covalently bonded to the prior structure, this may cause trouble. Right now, this keyword can only be used together with*NATINT**CASTEP job system*: tells the program to use the specified`CASTEP`executable to calculate energies and forces with input files based on the system name*system*. Periodic boundary conditions are assumed, so projection is not performed to remove overall rotation. For a finite system without periodic boundaries use*CASTEPC*instead of*CASTEP*(see below).*job*is a string in quotes that specifies the system call required to run the`CASTEP`executable. OPTIM will add a line with `elec_restore_file' to the`param`file after the first call to obtain the CASTEP energy and gradient. This saves a great deal of cpu time in subsequent CASTEP steps. However, it means that the final param file is altered, and you will need to remove the elec_restore_file line from the`param`file to restart the job if valid wavefunction files are not present in the working directory. CASTEP will fail and stop if the wavefunction read fails. Note that you cannot restart a job with a different number of nodes using saved wavefunctions! It is also necessary to specify the atoms in order of increasing atomic number, since otherwise they are reordered by`CASTEP`. There is now a check for this in`OPTIM`. The*system*.cell file is saved in*system.*cell.old in each call to potential before CASTEP is run. The geometry at the start of each Rayleigh-Ritz optimisation is saved in*system*.cell.save. To restart a transition state search the*system*.cell.save should generally be used. The*PARALLEL*keyword is no longer needed, since the number of processors can be specified in*job*if necessary: CASTEPC 'srun -N 1 -n 10 castep.mpi' 'qge' For an interactive run on nest mpirun works: CASTEPC 'mpirun -np 10 castep.mpi' 'qge' For a serial run on nest: CASTEPC 'castep.serial' 'qge' sbatch runs on nest require: module add gcc/7.5.0 module add mpi/openmpi/gnu7/4.0.5 module add castep/19.1/intel17-openmpi-gnu7For a

*CASTEP*normal mode analysis set*STEPS 0*,*MASS*,*ENDHESS*, and*ENDNUMHESS*in`odata`. The Hessian eigenvalues and normal mode frequencies are printed to standard output automatically. Check`pertable.f`first to make sure that the atomic mass is known for all the elements in your system. The frequency conversion assumes that the units of energy and distance are electron volts and Å. If*DUMPVECTOR ALLVECTORS*is set in`odata`then all the normal mode eigenvector components will be transformed to the Cartesian basis from the mass-weighted Cartesian basis. The components printed in the`vector.dump`file for normal mode*γ*are then*A*_{αγ}/ with 1≤*α*≤3*N*for*N*atoms. Here we follow the notation in `Energy Landscapes' around p. 141: the matrix diagonalises the mass-weighted Hessian**h**, and the corresponding eigenvectors of**h**are orthonormal. As shown in equation (2.51) of `Energy Landscapes', the relative displacements for Cartesian coordinate*X*_{α}are then*A*_{αγ}/, as printed in the`vector.dump`file. Hence, to put kinetic energy of magnitude*k*_{γ}into motion corresponding to normal mode*γ*requires Cartesian velocities = ±*A*_{αγ}, choosing either the plus or minus sign consistently for a given mode*γ*.*CASTEPC job system*: tells the program to use the new`CASTEP`to calculate energies and forces with input files based on the system name*system*. In this case the system is assumed to be a cluster, so that both translational and rotational degrees of freedom correspond to zero Hessian eigenvalues at a stationary point.*job*is a string in quotes that specifies the system call required to run the`CASTEP`executable. If*MASS*and*DUMPVECTOR ALLVECTORS*are set in`odata`then the normal mode frequencies will be printed in wavenumbers, and the normal mode eigenvector components will be transformed to the Cartesian basis from the mass-weighted Cartesian basis. It is necessary to specify the atoms in order of increasing atomic number, since otherwise they are reordered by`CASTEP`. There is now a check for this in`OPTIM`. The*PARALLEL*keyword is no longer needed, since the number of processors can be specified in*job*if necessary. Examples for mek-quake, darwin and zippo:CASTEPC 'mpirun /home/wales/bin/castep' 'qge' CASTEPC 'mpirun -np 64 -machinefile machine.file /home/dw34/bin/castep.mpi /home/dw34/bin/castep.mpi' 'qge' CASTEPC 'srun -p sca -n 36 /home/wales/bin/castep' 'qge'

For a

*CASTEP*or*ONETEP*normal mode analysis set*STEPS 0*,*MASS*,*ENDHESS*, and*ENDNUMHESS*in`odata`. The Hessian eigenvalues and normal mode frequencies are printed to standard output automatically. Check`pertable.f`first to make sure that the atomic mass is known for all the elements in your system. The frequency conversion assumes that the units of energy and distance are electron volts and Å. If*DUMPVECTOR ALLVECTORS*is set in`odata`then all the normal mode eigenvector components will be transformed to the Cartesian basis from the mass-weighted Cartesian basis. The components printed in the`vector.dump`file for normal mode*γ*are then*A*_{αγ}/ with 1≤*α*≤3*N*for*N*atoms. Here we follow the notation in `Energy Landscapes' around p. 141: the matrix diagonalises the mass-weighted Hessian**h**, and the corresponding eigenvectors of**h**are orthonormal. As shown in equation (2.51) of `Energy Landscapes', the relative displacements for Cartesian coordinate*X*_{α}are then*A*_{αγ}/, as printed in the`vector.dump`file. Hence, to put kinetic energy of magnitude*k*_{γ}into motion corresponding to normal mode*γ*requires Cartesian velocities = ±*A*_{αγ}, choosing either the plus or minus sign consistently for a given mode*γ*.*CHARMM*: specifies that the CHARMM potential is used. An auxiliary file`input.crd`is required.*CHARMM*must be the last OPTIM directive in the`odata`file. The remaining content of`odata`consists of CHARMM keywords and setup information.*CHARMMDFTB*: specifies that the CHARMM SCC-DFTB potential is to be used, and disables updates of the nonbonded list. This assumes you are using a fully QM system. If you are using a QM/MM setup, you should not use this keyword! Note that SCC-DFTB can only be used with CHARMM35.*CHARMMNOTUPDATE*: When using a very large cutoff, turn off nonbond list updating entirely.*CHARMMTYPE topfile paramfile*:*topfile*and*paramfile*are the common CHARMM top and param files , e.g., `toph19_eef1_perm.inp' and `param19_eef1_perm.inp'.*CHDEBUG EDEBUG*: produces more CHARMM related printing. Turned off by default. If EDEBUG is given as argument, after each CHARMM energy call the energy is decomposed and the components printed. Produces a lot of output!*CHECKD n*: for*n*= 1 (the default) prints numerical and analytical gradients for the starting coordinates, then exists. For*n*= 2, do the same for second derivatives. For*n*= 0 simply print the energy and exit.*CHECKINDEX nevs ceig nevl*: instructs the program to check the Hessian index after a BFGS minimisation or BFGS hybrid transition state search. This keyword also works with*NOHESS*. The parameters are the same as for*BFGSTS*below, and need not be set if they have already been specified by that keyword.*CHECKCHIRALITY*: checks that no inversion of a chiral centre happens. Residues can be L or D, but should remain in the same enantiomeric state during the simulation. CHECKCHIRALITY is always turned on for CHARMM, AMBER9 and NAB, i.e. this line is not needed in the*odata*file.*CHECKCONT*: if*CHECKINDEX*is specified then*CHECKCONT*instructs the program to take a pushoff and continue if convergence to a stationary point with the wrong Hessian index is detected.*CHECKGRAD diff*: calculate numerical two-sided first derivatives using displacement*diff*and compare with analytical values. Then stop.*CHECKHESS diff*: calculate numerical two-sided second derivatives using analytical first derivatives and displacement*diff*for comparison with analytical values. Then stop.*CHECKNEGATIVE*: if set then in**bfgsts**we backtrack and reduce the maximum step size if the smallest non-zero eigenvalue is positive. If the product of the scale factor with the maximum eigenvector-following step size and with the maximum LBFGS tangent space minimisation step size falls below the minimum value of the maximum step size set by*MINMAX*then the transition state search is aborted.*CHECKOVERLAP x*: if set then in**bfgsts**we backtrack and reduce the maximum step size if the magnitude of the dot product between the eigenvector corresponding to the uphill direction for the current and previous steps falls below*x*(default 0.1). If the product of the scale factor with the maximum eigenvector-following step size and with the maximum LBFGS tangent space minimisation step size falls below the minimum value of the maximum step size set by*MINMAX*then the transition state search is aborted.*CHECKREP n x*specifies the interval for updating the neighbour list for repulsive terms when*INTCONSTRAINT*is used.*n*is the interval for checking the neighbour list in terms of minimisation cycles for the constraint potential, default 10, and*x*is the multiple of the repulsive cutoff distance for which sites are included in the list, default 2.0. See also*CONINT*,*CONCUTABS*,*INTFREEZE*,*MAXCON*,*INTIMAGE*, and*INTCONSTRAINT*.*CHINTERPOLATE bint sint DNEB*: specifies the interpolation between endpoints for CHARMM. Following specifications are possible: CHINTERPOLATE BC SC does the interpolation for BHINTERP in Cartesians for the backbone and sidechains. That's the default for BHINTERP, which in this case also works without that line. CHINTERPOLATE BC SI does the interpolation for BHINTERP in Cartesians for the backbone and in Internals for the sidechains. CHINTERPOLATE BI SI does the interpolation for BHINTERP in Internals for the backbone and sidechains. CHINTERPOLATE BC SC DNEB does the interpolation for DNEB in Cartesians for the backbone and sidechains. That's the default for DNEB, which in this case also works without that line. CHINTERPOLATE BC SI DNEB does the interpolation for DNEB in Cartesians for the backbone and in Internals for the sidechains. CHINTERPOLATE BI SI DNEB does the interpolation for DNEB in Internals for the backbone and sidechains. The Internals are the primitive CHARMM internal coordinates. If you would rather like to use the natural internals, you have to use the INTINTERP keyword*CISTRANS*: allows cis-trans isomerisations for CHARMM, AMBER9 and NAB.*CLOSESTALIGNMENT*: specifies a job in which the structure supplied in the`finish`file is optimally aligned with the first set of coordinates given as input, the minimized distance is printed, and the aligned`finish`coordinates are dumped in an appropriate format (`aligned.crd`for CHARMM,`aligned.rst`for AMBER/NAB and`aligned`for everything else).*CLASSICALRATES temp1 temp2 tempstep*: Don't mix wit CALCRATES and READPATH, which are obsolete.*CLSTRING*: Use the climbing string method for saddle point search. (See Ren and Vanden-Eijnden, J. Chem. Phy., 138, 134105, 2013.) Should be used in conjunction with the GROWSTRING keyword to set parameters. Set EVOLVESTRING keyword to be true implicitly. The whole process will converge when the RMS of the last image meets the converge criterion.*COLDFUSION thresh*: if the energy falls below threshold*thresh*then cold fusion is assumed to have occurred and geometry optimisation stops.*COMMENT*or*NOTE*: the rest of the line is ignored.*CONCUTABS x*specifies the cutoff for the constraint potential when*INTCONSTRAINT*is used. Distances that deviate from the reference value by less than*x*, default 0.15, are not penalised by the constraint potential. See also*CONINT*,*CHECKREP*,*INTFREEZE*,*MAXCON*,*INTIMAGE*, and*INTCONSTRAINT*.*CONNECT n*: find a min-sad-min-^{ ... }-min sequence connecting the initial minimum in`odata`(or auxiliary files for CHARMM, UNRES, etc.) to the final minimum in`finish`, giving up if more than*n*transition states are needed (default*n*=100).*CONNECT*generally needs to be augmented by other keywords to specify how the transition state geometries should be guessed (*NEB*,*NEWNEB*,*FIXD*or*GUESSTS*), how the transition state searches should be performed (*SEARCH 2*or*BFGSTS*, with or without*NOHESS*,*NOIT*etc.), and how that pathways should be calculated (*SEARCH 0,*6 or 7,*BFGSMIN*,*RKMIN*or*BSMIN*). A summary file will be produced if*DUMPPATH*or*DUMPALLPATHS*is specified. An xyz file for the overall path will be printed to`path.xyz`and the energy as a function of the path length is printed to`EofS`. The corresponding xyz and energy files for the individual steps in the path are numbered path.*n*.xyz and EofS.*n*for transition state*n*. This keyword should NOT be used unless there's a really good reason - use*NEWCONNECT*instead.*CONSEC nstart nend nstart nend etc.*: construct linearly interpolated, internal coordinate transition state guesses and apply the stopping criterion in a*CONNECT*run over a chosen segment of protein specified by pairs of residue numbers (*nstart,nend*). Up to ten distinct sections can be chosen.*CONINT*specifies that terms for internal minimum distances should be included in the energy and gradient for the auxiliary interpolation potential when*INTCONSTRAINT*is specified. See also*CONCUTABS*,*CHECKREP*,*INTFREEZE*,*MAXCON*,*INTIMAGE*, and*INTCONSTRAINT*.*CONVERGE x y NOINDEX*: change the default convergence conditions for eigenvector-following and second order steepest-descent calculations described in §5. If one number is supplied then convergence depends only upon the maximum unscaled step falling below the specified value (and the right number of negative Hessian eigenvalues). If two numbers are supplied the second is the required threshold for the RMS force which must also be satisfied. If the string*NOINDEX*is present then the Hessian index isn't checked.*COPYRIGHT*: prints copyright information.*CPMD system*: tells the program to use CPMD to calculate energies and forces with input file*system*; bulk boundary conditions.*CPMDC system*: tells the program to use CPMD to calculate energies and forces with input file*system*; cluster boundary conditions.*CPPNEB*: specifies that the C++ implementation of the DNEB algorithm should be used. For this keyword to work, you must first download the C++ source code into OPTIM/cppneb/external (running the script OPTIM/source/setup.sh does this automatically). You must also compile OPTIM with the WITH_CPPNEB option set, and then use the executable OPTIM_CPPNEB. NOTE: the C++ code expects that the variable NEBK will be set to the value of half the actual spring constant. If you are translating between the Fortran and C++ implementations of DNEB, you will need to adjust your NEBK accordingly.*CUBIC*: if the three box lengths are equal to start with in a*PV*run, and the keyword*CUBIC*is included, then a cubic box is maintained.*CUBSPL*: For the growing string or evolving string double-ended transition state search methods, use a cubic spline interpolation between the image points.*CUDA potential*: specifies a GPU run. Setting*potential*to 'A' specifies the AMBER12 potential. See the group wiki for further information.*CUTOFF rcut*: Specify that the potential should go be zero for atom separations larger than rcut. This is not suppored for all potentials. (For some potentials rcut is passed using the PARAMS keyword.)*D5H x*: add a decahedral field of strength*x*to the potential.*DB epsbb epsab sigmabb sigmaab muD E*: calls a finite system of dipolar Lennard-Jones dumbbells [24], where the electric field of strength*E*can be optionally present. The field, if present, is along the space-fixed z-direction.*ε*_{aa}and*σ*_{aa}are both set to unity by default.*μ*_{D}is the dipole moment;*ε*'s and*σ*'s correspond to the Lennard-Jones parameters.*DCHECK ON/OFF*: turns on/off warning messages when atoms approach to within 0.5 distance units. Default is*ON*.*DEBUG*: causes unscaled steps, gradients, Hessian eigenvalues and summary information to be printed every cycle for*SEARCH*0–7 runs. Turned off by default. Also produces much more printing for individual steps in*CONNECT*runs.*DESMAXAVGE E*: specifies a maximum average energy, such that double-ended search methods will not stop until the average energy of the images is below*E*.*DESMAXEJUMP E*: specifies a maximum energy jump, such that a particular image step in a double-ended search method is skipped if the starting energy of that image is below 0 and the energy increases by more than*E*. Particularly useful when the*DESMINT*keyword is set. Recommended value 1.0×10^{4}.*DESMDEBUG*: Produces extra printing for the double-ended transition state search method runs (DNEB, GS or ES).*DF1*: specifies a binary 2D potential. The first*N*/2 atoms have unit radius and the rest have radius 1.4, with a cutoff for each pair type at the average radius. The keyword*2D*must also be specified, along with a*PARAMS*line to specify two box-lengths. Initial work uses box lengths of 3.31437171 for a number density of 0.9.*DFTB*: specifies that the tight-binding code of Walsh and Wales[25] is used.*DFTBP*: specifies that the DFTBP (SCC-DFTB+) code is used. The required files are*dftb_in.hsd*and the relevant Slater-Koster parameter files (*.skf) for each atomic pair in the system under study. These SK files can be downloaded from: https://dftb.org/parameters/download/. The geometry should always be specified in the*dftb_in.hsd*file and can also be read from a*start*file if needed.To build DFTBPOPTIM either use Intel and an mkl library, or GCC. Other modules may interfere. This combination works on nest for Intel:

`ifort/64/2020/4/304, mkl/64/2022/0/0, cmake/3.23.2`.For ifort the icc compiler needs to be specified as well:

`FC=ifort CC=icc CXX=icc cmake ∼/softwarewales/GMIN/source/ -DWITH_DFTBP=yes`If using GCC, a system BLAS needs to be used. Depending on the machine, CMake may be able to find one, or you may have to specify one yourself. This combination of modules works on nest:

`gcc/12.2.0, cmake/3.23.2`,with a configure line of

`cmake ∼/softwarewales/GMIN/source/ -DWITH_DFTBP=yes -DWITH_MYBLAS=no -DBLAS_LIBRARIES=/usr/lib64/libopenblas.so.0`To build DFTBP standalone in the DFTBP directory use

`FC=ifort CC=icc cmake -DCMAKE_INSTALL_PREFIX=/home/wales/softwarewales/DFTBP/_build -B _build .`then

`cmake –build /home/wales/softwarewales/DFTBP/_build – -j`then

`cmake –install /home/wales/softwarewales/DFTBP/_build`*DISTCON file*: specifies a general atom-atom harmonic distance constraint potential, which is added to the underlying potential.*file*is a file containing a list of atom pairs, the reference distance, and the force constant used in the harmonic term that penalises deviation from the reference separation. For example

367 393 2.27 1.01D3

372 385 2.65 1.02D3

*DGUESS dguess1 dguess2 dguess3 dguess4*: initial guess for diagonal elements of the inverse Hessian, used whenever the BFGS optimiser is reset.*dguess1*is used in geometry optimisations,*dguess2*is used for minimisation in eigenvalue calculations,*dguess3*is used for DNEB optimisation steps, and*dguess4*is used for string method optimisation steps. The default values are*dguess1=dguess2*=0.1,*dguess3=dguess4*=0.001*DIJKSTRA [EXP/n/INDEX/DIHEDRAL n] [INTERP x EXP/n]*: specifies that the missing connection Dijkstra-based algorithm[26] should be used to choose minima for connection in cycles of*NEWCONNECT*. The edge weights are based on the smallest distance between minima exponentiated (for*EXP*) or raised to the integer power*n*; if*INDEX*is specified instead then the metric becomes the modulus of the difference between the positions of the minima in the order they were found. Alternatively, the additional keyword*INTERP*specifies an edge weight based on the highest energy difference found by a linear interpolation between the minima at regular spacings of*x*. If*n*is also specied then the metric is raised to the power*n*. The final*EXP*or integer*n*specifies whether this highest energy is exponentiated or raised to the power*n*to obtain the edge weight.*DIHEDRAL*specifies an alternative metric for AMBER12 or AMBER20 based on dihedral angles. Here we sum the sine of the difference in dihedral angles for two structures divided by two, squared: sin^{2}*θ*_{1}-*θ*_{2}/2.*DNEBEFRAC x*: allows more DNEB steps if the current DNEB energy value is greater than*DNEBFRAC*times the lowest value found so far. Can be useful to prevent premature DNEB exit if we happen to be going through a phase with bad geometries. A maximum of ten times the maximum iterations parameter is permitted.*DNEBPATH*: creates`path.info`files based on the DNEB images without any further refinement, so long as the*CONVERGE*and*BFGSMIN*thresholds are set to huge values so that the images satisfy the RMS gradeint convergence condition. Local maxima in the set of images are taken as transition states, and local minima on either side are assigned as the connected `minima'. In DPS runs based on this approach we may have DNEB pathways with endpoints that are local maxima. In this case the image is added as both the fake transition state and the connected minimum.*DOINVERSION*: forces inversion check of structures for distance metric in**minpermdist**, even for biomolecules.*DOUBLE*: adds a double-well potential as per*J. Chem. Phys.*,**110**, 6617, 1999. The energy and derivatives add to the potential specified by the atom type. Only atom type `LS' (not binary) has the 1,2 interaction removed as well. At low density some atoms may not interact with any others and problems result due to additional zero eigenvalues.*DQAGKEY n*: n (integer between 1 and 6) indicates the number of local integration points used for calculating cubic spline arc lengths in the string methods. Default value is 6, which corresponds to 30-61 points.*DRAG*: obsolete method that transforms one end point into another by progressively increasing a spring potential that attracts the system to the final geometry.*DUMPALLPATHS*: prints a summary of every min-sad-min path found during a*CONNECT*or*NEWCONNECT*run to file`path.info`. For each stationary point the energy, point group order and symbol, Hessian eigenvalues and coordinates are given. Hessian eigenvalues are computed for all stationary points. This min-sad-min format corresponds to the*TRIPLES*keyword in the PATHSAMPLE program.*DUMPBESTPATH*: after the last cycle in*NEWCONNECT*another Dijkstra analysis is run, the best path according to this analysis is then written to`path.info`. Useful to prevent a fast increase in the database size in PATHSAMPLE.*DUMPFRQS*: if the frequency of a stationary point is calculated, it is written to a file`frqs.dump`. The keyword is mainly meant for the*GETMINFRQS*and*GETTSFRQS*options in PATHSAMPLE. It requires that*ENDHESS*or`ENDNUMHESS`are used.*DUMPDATA*: creates a file`sp.data.info`in PATHSAMPLE`min.data`or`ts.data`format for the minimum or transition state found following a minimisation or ts search. The connectivity information will not be available for a transition state; it is better to create`path.info`file and use`PATHSAMPLE`keyword*ADDPATH*if a full transition state entry is required.`DUMPDATA`was originally intended for setting up a discrete path sampling initial path run by creating entries for the two endpoint minima. Now it can also be used with the*CHECKTS/GETTSFRQS*procedure in`PATHSAMPLE`.*DUMPDATA_MACHINE ndof*: to be used instead of*DUMPDATA*when lots of data will be produced (e.g. using*MULTIJOB*). The normal output from*DUMPDATA*is split into two files. The energy, frequency log product, point group order and moments of inertia of each minimum found are written to`min.data.info`as normal (formatted output). The coordinates of the minima are written to an unformatted file`min.data.info`, which readable only by the machine and therefore is quicker to read/write and takes up less disk space. Each minimum is written as a single record of length*ndof*, which is the number of coordinates (degrees of freedom) in the system.*DUMPEVALS*: dumps the hessian eigenvalues in file`evals.dump`, preceded by the energy, all on one line (hence it has*N*_{vars}+ 1 columns with*N*). With*MULTIJOB*you can obtain results for a set of configurations in one job.*DUMPINTEOS n*: creates the file`EofS.int`for QCI runs.*n*is the dump frequency.*DUMPINTXYZ n*: creates the file`int.xyz`for DNEB and QCI runs.*n*is the dump frequency.*DUMPMODE n1 n2 etc*: must be used with and below*DUMPVECTOR ALLVECTORS MWVECTORS*. Produces PDB files`mode.n1.pdb, mode.n2.pdb`etc containing information on the relative per atom and per residue displacement caused by that mode. This information can be visualised in VMD by colouring with the`Beta`(per residue) or`Occupancy`(per atom) options.*DUMPNEBEOS n*: creates the file`EofS.neb`for DNEB runs. This file is also created if*DEBUG*is set; the default is false.*n*is the dump frequency.*DUMPNEBPTS*: saves points for DNEB every iteration.*DUMPNEBXYZ n*: creates the file`neb.xyz`for DNEB runs. This file is also created if*DEBUG*is set; the default is false.*n*is the dump frequency.*DUMPPATH*: prints a summary of the min-sad-min-^{ ... }-min path produced by*CONNECT*or*NEWCONNECT*to file`path.info`. For each stationary point the energy, point group order and symbol, Hessian eigenvalues and coordinates are given. Hessian eigenvalues are computed for all stationary points. The`path.info`format for*DUMPPATH*is now the same as for*DUMPALLPATHS*, i.e. min-sad-min then min-sad-min, etc.*DUMPSP*: specifies that information for all the stationary points located should be dumped in PATHSAMPLE`min.data`/`ts.data`format.*DUMPSTRUCTURES*: specifies that final structures should be dumped for the Amber 9 runs into pdb, Amber restart and xyz formats.*DUMPVECTOR [ALLSTEPS] [ALLVECTORS [MWVECTORS]]*: if present the Hessian eigenvectors will be written to file`vector.dump`after each OPTIMisation step, preceded by the corresponding eigenvalue for each one. The eigenvectors corresponding to zero eigenvalues are excluded. For hybrid eigenvector-following/BFGS transition state searches only the results corresponding to the smallest non-zero eigenvalue are dumped. The default is to dump only the vector corresponding to the smallest non-zero eigenvalue for the last step. If*ALLSTEPS*is present then vectors are dumped at every step. If*ALLVECTORS*is present then all the vectors corresponding to non-zero eigenvalues are dumped, rather than just one of them. If*MWVECTORS*is also specified, the vectors dumped are the normal modes, using appropriate mass weighting and the`vector.dump`file will contain the vibrational frequencies (in wavenumbers) rather than the eigenvalues. Two additional output PDB files are also be produced.`totalmodes.pdb`contains per atom and per residue displacement information resulting from a vector sum of ALL normal modes of non-zero frequency.`weightedmodes.pdb`contains similar information for a Boltzmann weighted (by frequency) vector sum of all normal modes. See*DUMPMODE*for information on how to visualise this data. Note that the Boltmann weighting is done with kT=207.11 cm^{-1}(corresponding to room temperature) unless otherwise specified by the*KTWN*keyword. A third output file is also produced if*KTWN*is specified.*ALLSTEPS*and*ALLVECTORS*can be present in either order.*EDIFFTOL x*: specifies the energy difference used to identify permutational isomers in*CONNECT*and*NEWCONNECT*runs. Default is*x*= 10^{-9}.*EFIELD x*: specifies that an electric field along the*z*axis should be included with magnitude*x*V/Å. For use with TIPnP potentials.*EFSTEPS n*: prints the unscaled steps in the Hessian eigenvector basis every*n*steps—turned off by default.*ENDHESS n*: calculate analytical Hessian and normal mode frequencies at end of run. To obtain frequencies for*UNRES*,*CASTEP*and*ONETEP*you must specify both*ENDHESS*and*ENDNUMHESS*. For an eigenvalue analysis, with no geometry optimisation, specify*STEPS 0*. To have the Hessian eigenvalues printed to standard output you must specify the*DEBUG*keyword, except for*AMH*,*CASTEP*and*ONETEP*, where they are printed automatically.*n*specifies the number of Hessian eigenvalues to be calculated (starting from the lowest), which defaults to all.*ENDNUMHESS*: calculate numerical Hessian and normal mode frequencies at end of run. Required if*DUMPPATH**or ENDHESS*is specified for an*UNRES*run, in which case it's an internal coordinate Hessian. Also required for a*CASTEP*or*ONETEP*normal mode analysis, which also requires*STEPS 0*and*ENDHESS*to be set. To have the Hessian eigenvalues printed to standard output you must specify the*DEBUG*keyword, except for*AMH*and*CASTEP*, where they are printed automatically.*ENDNUMHESS2 delta*: calculate numerical Hessian and normal mode frequencies at end of run. This keyword is different from*ENDNUMHESS*in that a higher order finite difference is used (Richardson extrapolation), which takes twice as long, but should be more accurate. The optional parameter*delta*is the finite difference displacement, default value 10^{-6}.*EIGENONLY ceig cover*: instruct the program to perform a search that only estimate the lowest eigenvalue and the corresponding eigenvector.*ceig*is a double precision parameter that sets the convergence criterion for the calculation of the smallest non-zero Hessian eigenvalue. If*NOHESS*is set*ceig*is compared to the RMS `force' corresponding to the Rayleigh-Ritz expectation value that is minimised to get the smallest eigenvalue. If the Hessian is used via iteration or*NOIT*then*ceig*is compared to the percentage change in the eigenvalue between successive steps. The default value is 1.0, which is more appropriate to the latter case. Smaller values are probably necessary in BFGS/BFGS calculations.*cover*is a double precision parameter that sets the convergence criterion. The search coverges when the magnitude of the dot product of the estimated mode with the target mode is greater than "cover". The target mode is read from file "target.vector", the first line of which supposes to be the eigenvalue but not read actually. the following lines are read as the target mode. "cover" doesn't have a default value. It works only if it is seted and the parameter "ceig" is then out of function.*ERROREXIT*: indicates that the program should halt on error.*EXTRAPERM*: for use with PERMDIST when allowing the full permutation group is too permissive. Allows the custom specification of what permutations to allow. For example, when dealing with rigid bodies, the body might have a rotation. The permutations are listed in the file extra_perm.allow, which must be present in the working directory. The first line must specify the number of groups in the file. This is followed by the specification of the groups, each of which has the following format:<Number of permutations in the group><Number of atoms in the group>

<Identity permutation>

<Other permutation>

.

.

.

Each group should probably be a full symmetry group in the mathematical sense, but this is not checked. For example, if there were two rigid bodies that had the form of pentagonal bipyramids, with an allowed five fold rotation axis interchanging the radial atoms, that were 3-7 in each body, extra_perm.allow might be:

2

5 5

3 4 5 6 7

4 5 6 7 3

5 6 7 3 4

6 7 3 4 5

7 3 4 5 6

5 5

10 11 12 13 14

11 12 13 14 10

12 13 14 10 11

13 14 10 11 12

14 10 11 12 13

*EVCUT x*: sets a cutoff value for eigenvalues. Eigenvalues of magnitude less than*x*are treated as zeros and steps along such directions are omitted.*EVOLVESTRING*: use the evolving string method based on the zero-temperature string method of E et al [19] for double-ended transition state searches. Should be used in conjunction with the*GROWSTRING*keyword to set parameters.*EXTRASTEPS x*: obsolete; extra minimisation steps are allowed for*CHARMM*runs proportional to the separation between two minima multiplied by*x*.*FILTH n*: specifies an integer variable,*n*, to distinguish output files in parallel landscape jobs. This keyword will be retired shortly in favour of the new command line specification of file name extensions.*FIXAFTER n*: specifies that*FIXIMAGE*should be set permanently after step*n*. This effectively freezes the interacting images in different supercells for calculations with periodic boundary conditions.*FIXATMS*: For the GS and ES double-ended transition state search methods, avoid overall translation and rotation by fixing all three coordinates of one atom, confining another atom to a line, and a third atom to a plane for all steps.*FIXD t12fac dthresh*: transition state search using hard sphere moves. A random velocity vector is assigned and the first hard sphere collision is located. If*t12fac*≤1 then the system is moved through a fraction*t12fac*of this first collision time; the default value is 1. If*t12fac*> 1 then the two atoms are moved half way between the entrance and exit of their collision, but their separation is rescaled to unity. See also RANSEED. Used in*CONNECT*procedure only if*FIXD*is set and the two minima to be connected are closer than*dthresh*.*FRACTIONAL*: specifies fractional coordinates to be used in box length optimisation for constant pressure runs using*PV*.*FREEZE n1 n2 etc.*: specifies that atoms*n1, n2,*etc. should be frozen. Only works for LBFGS minimisation and BFGSTS if 3 or more non-linear atoms are frozen. Frozen atoms may also be specified in a file`frozen`. The first line of the file should contain the number of frozen atoms. Subsequent lines contain the atom indices to be frozen.*FREEZERES n1 n2 etc.*: specifies that residues*n1, n2,*etc. should be frozen.*FREEZEGROUP centreatom radius mode*: specifies that all atoms outside (*mode = GT*, the default) or within (*mode = LT*) a sphere of radius*radius*centred on atom*centreatom*should be frozen. Also produces a file*frozen.dat*containing the corresponding single atom FREEZE commands.*FREEZENODES tol*: For the double-ended transition state search methods (NEB, DNEB, GS, ES), at each step freeze those nodes for which the RMS perpendicular force, as a fraction of the RMS force over all the images, is less than*tol*. over all the images.*FREEZERANGE n1 n2*: freezes all atoms in the range of atom numbers n1 to n2.*FRQCONV x*: Specify a conversion factor*x*to be applied to Hessian eigenvalues and frequencies before they are printed, either in`min.data.info`files as the log product of Hessian eigenvalues (log product of square angular frequencies) or in`path.info`files as the actual frequencies. The default factor*x*is 1, which is appropriate for systems where all atoms have the same mass. In this case, frequencies are given in internal units of where*ε*is the energy unit,*m*the mass unit and*σ*the length unit for the system in question. For more complex systems (particularly external potentials such as*AMBER*) it may be more convenient to convert to SI units before printing out. The most common potentials have default values of*x*hard-coded into`keywords.f`, but specifying this keyword will override all defaults if you wish to work in a non-SI unit system. For more detail on how this keyword works, check the comments in`keywords.f`.*GAMESS-UK system exec*: potential will be generated by GAMESS-UK.*system*is a string to identify the system and*exec*is the name of an executable that will generate a GAMESS-US input deck from a points file. If*exec*is omitted its name is assumed to be*editit.system*.*GAMESS-US system exec*: potential will be generated by GAMESS-US.*system*is a string to identify the system and*exec*is the name of an executable that will generate a GAMESS-US input deck from a points file. If*exec*is omitted its name is assumed to be*editit.system*.*GAUSSIAN*: tells the program to read derivative information in Gaussian92 format. This should not be used; it has been superceded by*GAUSSIAN09*and friends.*GAUSSIAN03 charge multi*: potential will be generated by Gaussian03.*charge*is the total charge of the system.*multi*: is the spin multiplicity of the system. Note that Gaussian outputs energy derivatives in atomic units. OPTIM expects coordinates in Angstrom, and converts the units of the Gaussian derivatives. An example can be found in: http://www-wales.ch.cam.ac.uk/examples/OPTIM/*GAUSSIAN09 charge multi*: potential will be generated by Gaussian09.*charge*is the total charge of the system.*multi*: is the spin multiplicity of the system. Note that Gaussian outputs energy derivatives in atomic units. OPTIM expects coordinates in Angstrom, and converts the units of the Gaussian derivatives. An example can be found in: http://www-wales.ch.cam.ac.uk/examples/OPTIM/*GAUSSIAN16 charge multi*: potential will be generated by Gaussian16.*charge*is the total charge of the system.*multi*: is the spin multiplicity of the system. Note that Gaussian outputs energy derivatives in atomic units. OPTIM expects coordinates in Angstrom, and converts the units of the Gaussian derivatives. An example can be found in: http://www-wales.ch.cam.ac.uk/examples/OPTIM/*GEOMDIFFTOL x*: specifies the distance criterion used to identify identical isomers in*CONNECT*and*NEWCONNECT*runs. Default is*x*= 10^{-1}.*GLJ n1 n2 n3 etc.*: specifies general Lennard-Jones potential for any number of differ LJ species. The*ε*and*σ*parameters for all the different species should be specified as the lower diagonal blocks of the corresponding matrices on the following lines. For example, to specify a 13-atom cluster with three different species: GLJ 6 4 3 1.0 1.1 1.2 1.2 1.3 1.4 1.0 1.5 1.6 1.7 1.8 1.9*GOT*: Paul Whitford's Gō model potential.*GRADIENTS n*: causes the gradients along the Hessian eigenvectors to be printed every*n*cycles. Gradient printing is turned off by default.*GRADSQ gsthresh nspecial nallow*specifies optimisation of the modulus gradient with*nallow*second order steps at intervals of*nspecial*if the RMS force lies below*gsthresh*.*GRADTYPE type*specifies the gradient formulation to use with the*NEWNEB*keyword. The default is `*dneb*'; other allowed values are `*jnew*' (new implementation of neb by Jonsson), `*spr*' (full springs), `*jold*' (springs MEP-parallel component only, the original formulation), `*nper*' (springs MEP-parallel component (original formulation) + n% of perpendicular component), `*nper2*' (springs MEP-parallel component (original formulation) + n% of perpendicular component, possibly optimised) `*dneb2*' (same as `*dneb*', except spring gradient usage is more consistent). `*dihen*' (distance between images calculated in dihedral angle space; for use with CHARMM and UNRES), `*dnebu*' (DNEB for unres), `*dneb3*' (uses deviation from the average separation in the spring term instead of absolute distance),*GREATCIRCLE gcmxstp gcmxstp gcsteps gcconv*: obsolete; interpolation between two end points using a great circle in 3*N*-dimensional space.*GROWSTRING nimage iterd reparamtol growtol convtol mxstp*: specifies that double-ended transition state searches will be done using either the evolving string method (based on that described by E et al[19]) or the growing string method (based on that described by Peters et al[20]). The default is growing strings; if the separate keyword*EVOLVESTRING*is also specified, the evolving string method will be used instead.*nimage*and*iterd*specify the number of images and the maximal iterations per image to be used in the first connect run; for all subsequent connections these parameters are determined from the*NEWCONNECT*line. In the growing string case, the iteration density affects only the maximum iterations allowed after the string is fully populated with images. The string is reparametrised and the images redistributed whenever the ratio of actual inter-image distance to the desired distance falls below*reparamtol*for at least one segment. For growing strings, a new image is added to one side of the string whenever the RMS perpendicular force on one of the frontier images falls below*growtol*. The string is deemed to have converged if the RMS perpendicular force over all the images falls below*convtol*.*mxstp*refers to the maximum allowed step for each image during the optimisation. The default is a linear interpolation between image points; use the*CUBSPL*keyword to switch this to a cubic spline interpolation.*GSMAXTOTITD itd*: Set the maximum total iteration density for the growing string method. This specifies the maximum evolution iterations allowed per total image number, including the iterations while the string is still growing. If*itd*is less than 0, then this parameter is turned off and there is no limit on the total iterations (this is the default).*GUESSPATH gsteps maxgcycles gthreshold maxinte*: obsolete; try to guess an interpolated path for sequential coordinate changes.*gsteps*is the number of step to be tried for each sequential coordinate.*maxgcycles*is the number of sweeps through pairwise exchanges*gthreshold*is the coordinate change above which sequential changes are considered.*maxinte is*the convergence criterion for the maximum allowed interpolated energy.*GUESSTS guessthresh*: use dihedral twisting in place of*NEB*for transition state guesses with*CONNECT*for CHARMM and UNRES.*HESSDUMP*: dump the Hessians for local minima and transition states in files`minhess.plus`,`minhess.minus`, and`tshess`. The Hessian is printed before each diagonalisation step that is used to produce entries in`path.info`files in subroutines**path**and ncutils. If more than one minimum-transition state-triple appears in the`path.info`file then the corresponding Hessians are simply concatenated in the`hess`files. Only works if*DUMPPATH*or*DUMPALLPATHS*are set.*HESSGRAD*: For the growing string or evolving string double-ended transition state search method, use the method described in the appendix of Peters et al[20] to calculate the Newton-Raphson search direction. Namely, the Hessian is approximated based on changes in the gradient, and the tangential component of -**Hf**^{⊥}is projected out. By default, the Hessian used is actually an approximation to the derivative matrix of*f*^{⊥}rather than the gradient.*HESSREAD nzeroRS nzeroTS*: nzero*=NFROZEN*3+6*HIGHESTIMAGE*: obsolete; only use the highest non-endpoint image in a double-ended*MECCANO*run.*HUPDATE nstart ninterval phi*: uses a Hessian update procedure instead of calculating the analytic second derivatives at every step.*nstart*is the first step at which analytic derivatives will be calculated; by default*nstart*=0, the Hessian is initialised to the identity and no analytic second derivatives are ever calculated.*ninterval*is the interval at which analytic Hessians are calculated; the default is 0, which means that no additional analytic Hessians are ever found. A transition state search starting from a minimum seems unlikely to work unless we calculate analytic Hessians at regular intervals including the first step. Update applied is*phi*times Powell[27] plus (1-*phi*) times Murtagh-Sargent. (See Bofill and Comajuan, J. Comp. Chem., 11, 1326, 1995.)*HYBRIDMIN nevs ncgmax1 ncgmax2 ceig mxstp nsteps evmax method nevl*: instructs the program to calculate pathways using hybrid minimisation.*nevs*is an integer that defines the largest number of iterations allowed in the calculation of the smallest Hessian eigenvalue; default 500.*ncgmax1*is an integer that defines the largest number of BFGS steps allowed in the subspace minimisation before the eigenvalue is deemed to have converged; default 10.*ncgmax2*is an integer that defines the largest number of BFGS steps allowed in the subspace minimisation after the eigenvalue is deemed to have converged; default 100. This parameter is ignored if*NOIT*is set. The eigenvalue is deemed to be converged if the modulus of the overlap between the corresponding eigenvector and that saved from the previous step exceeds 0.999 and we have the right number of negative eigenvalues.*ceig*is a double precision parameter that sets the convergence criterion for the calculation of the smallest non-zero Hessian eigenvalue. If*NOHESS*is set*ceig*is compared to the RMS `force' corresponding to the Rayleigh-Ritz expectation value that is minimised to get the smallest eigenvalue. If the Hessian is used via iteration or*NOIT*then*ceig*is compared to the percentage change in the eigenvalue between successive steps. The default value is 1.0, which is more appropriate to the latter case. Smaller values are probably necessary in BFGS/BFGS calculations.*mxstep*is the maximum initial step size allowed for the step along Hessian eigenvectors; it is adjusted dynamically using a trust radius scheme (see*TRAD*).*nsteps*is the maximum number of steps before returning and switching to LBFGS minimisation. The routine will also exit and switch to LBFGS if the smallest non-zero Hessian eigenvalue exceeds*evmax*.*method*can be either `EF' or `PM', specifying eigenvector-following or Page-McIver steps. The number of non-zero Hessian eigenvalues and corresponding eigenvectors determined is one by default, but any value can be specified using*USEEV*.*nevl*is an integer that defines the largest number of iterations allowed in the calculation of the largest Hessian eigenvalue; default 100. Not needed if*NOHESS*of*NOIT*is set.*IH x*: add an icosahedral field of strength*x*to the potential.*INDEX n*: initiates a search for a saddle of index*n*if*SEARCH*2 is specified. See also*KEEPINDEX*. Also works with*BFGSTS*up to a maximum of index 50, but*NOIT*must be set and a Hessian is needed.*INE_NEW sttsrmsconv st_tsstep lan_dist lanstep lanconv lanfactor*: Using "inexact newton method" to accelerate the convergence of TS search at the end of the climbing string method. sttsrmsconv sets is the convergence criterion for the root-mean-square gradient. st_tsstep sets the maximum number of steps allowed to move. lan_dist sets the small parameter used to approximate the matrix-vector multiplication. lanstep sets the maximum iteration number of Lanczos. lanconv sets the stop criterion of Lanczos process. lanfactor sets a scale parameter to control the step size of step vector.*INSTANTONOPT nimageinst distortinst deltainst temperature*: Instanton optimisation with*nimageinst*is the number of images used in the optimisation,*distortinst*the amount of distortion from the classical transistion state to obtain the initial instanton path, and*deltainst*the offset to calculate the instanton Hessians. Example parameters are: nimageinst=1, distortinst=0.4, deltainst=0.01. The*temperature*for the tunnelling process is specified only with this keyword.*INSTANTONRATE nimageinst*: Instanton rate calculations. For more details see 14.*INSTANTONSTARTDUMP temperature*: Dumps the initial files for instanton rate calculations. The file input.xyz contains either the transistion state (saddle point) or the reactant state (minimum). For more details see 14.*INTEPSILON x*: specifies the value of the*ε*parameter for diagonal shifts in the sparse internal coordinate transformation. The default is*x*= 10^{-6}.*INTERPBACKTCUT c*: the internal coordinate back-transformation convergence cutoff used for interpolations. Default value is 1.0×10^{-8}*INTERPCHOICE*: when used with the*INTINTERP*keyword, specifies that linear interpolations between endpoints are done with both internal and Cartesian coordinates. The interpolated path with the lower maximum energy is then used to start the double-ended search method.*INTERPSIMPLE*: when used with the*INTINTERP*keyword, specifies that an internal coordinate interpolation is done with the same number of image points as desired for the double-ended search methods. The resulting image points are converted directly to Cartesians. The Cartesian images will not necessarily be evenly distributed along the path.*INTINTERP nim*: specifies that internal coordinates are to be used for interpolating between endpoints. Automatically uses natural internal coordinates. Does a linear interpolation with*nim*images, then places the required number of Cartesian image points at approximately equal arclengths along the resulting path. Default value of*nim*is 100. Turns off the*DESMINT*keyword.*INTMIN*: specifies that internal coordinates be used in calls to**mylbfgs**, including minimisation in the tangent subspace for hybrid eigenvector-following. The algorithm used is that of Németh*et al.*[28] Not recommended.*INTMINPERM*: when aligning endpoint structures, permute the permutable atoms to minimise the distance in individual torsion angles. Use only with*INTINTERP*or*DESMINT*.*INTPARFILE file*: Use a parameter file to specify the internal coordinates for amino acids, rather than generating them automatically.*INVERTP*: specifies the inverted potential. The energy and all derivatives are multiplied by -1. This converts searches for the highest index saddles into minimisation. However, it is only likely to work for bounded potentials.*KEEPINDEX*: specifies that*INDEX*is set equal to the number of negative Hessian eigenvalues at the initial point.*KTWN x*: for use with*DUMPVECTOR ALLVECTORS MWVECTORS*- sets kT in cm^{-1}to x. The default value is 207.11 cm^{-1}. If KTWN is specified, an additional output file,`thermalmodes.pdb`is produced during a normal mode analysis containing per atom and per residue displacement information resulting from a Boltzmann weighted (by frequency) vector sum of all normal modes whose frequencies are less than kT. This information can be visualised as described for*DUMPMODE*.*LANCZOS*: obsolete; specifies that a Lanczos procedure should be used to find eigenvalues and eigenvectors. Lapack routine`DSYEVR`is now used throughout instead.*LJADD*: specifies an addressable LJ potential. A data file`epsilon`is required specifying the well depth parameter*ε*for all pairs of atoms, one per line. Choosing values according to nearest neighbours in a reference geometry can bias the system towards that configuration.*LJADD2 n*: specifies an addressable LJ potential for multiple copies of an*n*-particle cluster. The data file`epsilon`is required with*n*×*n*entries, one per line. These well depth parameters are then applied modulo*n*. For particles with the same address, only the repulsive part of the LJ potential is used.*LOCALPERMDIST thresh cutoff orbittol*: minimise distances between end points prior to DNEB interpolation using local alignment.*thresh*is used to define the tolerance for a `perfect' alignment in routine**minpermdist**, which is called for subsets of atoms rather than all at the same time for*PERMDIST*. The threshold used is actually the number of atoms in the permutable group in question times*thresh*. The routine**minpermrb**cycles through the permutable groups, calling**minpermdist**for each one, augmented by any other permutable groups that overlap, as for any groups with additional pair swaps, such as valine and arginine. Atoms that are equidistant from the permutable atoms in the two end points are also added to the set if the distance lies within a cutoff radius*cutoff*. They are added in increasing distance order, and removed one at a time if the resulting subsets of atoms cannot be aligned `perfectly' between the two endpoints. Using cutoffs of 2.5 and 5 Å gives different internal rotations for an arginine group, but with similar barriers. The default values are 0.1 and 5.0 for*thresh*and*cutoff*, respectively.*orbittol*sets the threshold for assigning atoms to the same orbit when analysing the standard orientation in routine**myorient**; default is 0.001. Requires the auxiliary file`perm.allow`to specify permutable atoms, otherwise all atoms are assumed to be permutable. The absence of a`perm.allow`file is considered a mistake for*CHARMM*runs. See also*LPERMDIST*, which effectively replaces*LOCALPERMDIST*.The first line of the

`perm.allow`file must contain an integer that specifies the number of primary groups of interchangeable atoms. The groups then follow, each one introduced by a line with two integers*p*and*s*that specify the number of permutable atoms in the primary group and the number of other sets of permutable atoms associated with the primary set.*s*may be zero. Each secondary set of permutable atoms has*p*members. The following line contains the indices of the*p*permutable atoms in the primary set and then the indices of the atoms in each of the*s*secondary sets, one set at a time.Scripts to generate allowed permutations automatically for CHARMM and AMBER are available from the group web site. It is essential to use symmetrised versions of the corresponding force fields! See the

*PERMDIST*keyword for example`perm.allow`file entries.*LOWESTFRQ*: specifies that the lowest positive eigenvalues associated with the Hessian and mass-weighted Hessian should be calculated and written to`min.data.info`. These eigenvalues can then be used in combination with*DUMMYTS*in PATHSAMPLE to estimate the energy and frequency factor associated with dummy transition states. The*LOWESTFRQ*keyword must appear in`odata.bhinterp`or`odata.bisect`for such jobs, along with*DUMPDATA*and*BHINTERP*or*BISECT*.*LPERMDIST n thresh cut orbittol*: provides the preferred local permutational alignment procedure.*n*is the maximum number of extra atoms to include in running**minperm**for each permutable group (default 11, a value that may be needed to treat phenylalanine), rather than treating the whole system at the same time, as for*PERMDIST*. The extra atoms that define the neighbourhood of the permutable group are added one at a time in order of their distance from the centre of coordinates of the group, averaged over the start and finish geometries. If the optimal aligned distance is greater than*thresh*(default value 0.5) then the atom is not included in the neighbour list. This procedure continues until there are*n*atoms in the neighbour list, or no more atoms within the cutoff distance*cut*, default 5.0. The parameter*orbittol*is the distance tolerance for assigning atoms to orbits in the**myorient**standard orientation routine, default value 0.06. This keyword requires the auxiliary file`perm.allow`to specify permutable atoms, otherwise all atoms are assumed to be permutable. The absence of a`perm.allow`file is considered a mistake for*CHARMM*runs.*MACHINE*: specifies that points should be saved in binary (machine) format instead of human-readable xyz. Default false.*MASS*: specifies the use of mass weighting for the steps; the output coordinates are not mass weighted.*MAXBARRIER x*:*x*specifies the maximum value for the smaller barrier height that is allowed to constitute a connection during the*DIJKSTRA*connection procedure. See also*MAXMAXBARRIER*to restrict the larger barrier height.*MAXBFGS x1 x2 x3 x4*:*x*specifies the maximum allowed step length in LBFGS minimisations,*x1*for normal minimisations,*x2*for Rayleigh-Ritz ratio minimisation,*x3*for putting structures in closest coincidence with**ministd**, and*x4*for NEB minimisations. Default values all 0.2.*MAXCON n*specifies the maximum number of distance constraints for any atom when*QCI/INTCONSTRAINT*is used. The default value for*n*is 4.*MAXERISE x1 x2*:*x1*is the maximum energy increase above which**mylbfgs**will reject a proposed step. The default is*x*= 10^{-10}, but a much larger value may be needed for CASTEP runs.*x2*performs the same function for the maximum rise in the Rayleigh-Ritz ratio during minimisation in**xmylbfgs**.*MAXFAIL n*: maximum number of failures to lower the energy allowed in a minimisation before giving up.*MAXGAP*: specifies that in*NEWCONNECT*runs only one connection attempt is made per cycle, corresponding to the minima separated by the largest gap.*MAXGROWSTEPS n*: For the growing string double-ended connection method, specify a maximum number of steps allowed before another image is added to the growing string. Default is 1000.*MAXIMFACTOR x*: this is the factor used in`output.f90`to identify local maxima for hybrid EF ts searches; the default is*x*= 10. It multiplies EDIFFTOL.*MAXLENPERIM x*: will stop the entire job if the total string length for the growing strings or evolving strings method goes above*x*times the total number of images. This usually means that something is going wrong with the string. Default is 1000.*MAXMAX x*: specifies the maximum value that the maximum step size is allowed to rise to. The default value is 0.5.*MAXMAX*is also used as the uphill step size in hybrid eigenvector-following transition state searches if the eigenvalue of the direction being followed is positive.*MAXMAXBARRIER x*:*x*specifies the maximum value for the larger barrier height that is allowed to constitute a connection during the*DIJKSTRA*connection procedure. See also*MAXBARRIER*to restrict the smaller barrier height.*MAXSTEP x1 x2*: specifies the maximum step size for eigenvector-following and steepest-descent calculations, default value 0.2. The precise implementation of this constraint depends upon the step scaling method employed (see §8).*MAXTSENERGY x*: maximum ts energy that is allowed to constitute a connection during the Dijkstra connection procedure. Paths are not calculated for transition states above this threshold, and entries are not created in the`path.info`file. Useful for*CHARMM*to ignore unphysical stationary points.*MBPOL*: the MBPol intermolecular potential for water.*MCBIAS*: Use a bias potential in the*MCPATH*sampling.*MCPATH2 T dmax start r bins nequil nmc prtfrq block over qmin qmax addref neglect tol*: parameters are as follows:*T*is the temperture,*dmax*is the distance constraint beyond which Monte Carlo steps are rejected,*start*specifies the starting configuration for the MC sampling (-1 for the first minimum, 0 for the transition state, 1 for the second minimum),*r*target acceptance ratio (step size is varied in equilibration phase),*bins*is the number of bins for the order parameter,*nequil*number of equilibration steps (discarded),*nmc*number of MC production steps,*prtfrq*print frequency,*block*size of blocks used in sampling (maximum size is the total number of frames),*over*number of frames in overlap region for blocks,*qmin*minimum value of order parameter,*qmax*maximum value of order parameter,*addref*not used, parameter to neglect bins with fewer visits than*neglect*times the largest number of visits (zero is usually OK),*tol*RMS convergence condition for WHAM fitting. See also the*PBS*keyword for distributing jobs for sampling independent blocks over cores.*MCPATHGW x1 x2*: variance of Gaussians used to smooth the probability distributions in path length and order parameter.*MECCANO mecimdens mecmaximages mecitdens mecmaxit meclambda mecdist mecrmstol mecstep mecdguess mecupdate*: obsolete; an interpolation between end points via rigid rods of variable length.*METRICTENSOR*: For use with RIGIDINIT only. Specifies that Hessian eigenvalues and eigenvectors will be calculated by solving the generalised eigenvalue problem based on the Metric Tensor, as described in Rühle*et al*, JCTC**9**, 4026 (2013). Without this keyword, the default method is that due to Pohorille*et al*, JCP**87**, 6070 (1987).*MIE_FIELD filename Rc Bx By Bz*: specifies a fixed substrate from superposition of Mie-type central force fields, each defined by*φ*(*r*) =*ε*- .*n*,*m*,*ε*,*σ*and coordinates of each Mie site must be provided in the file*filename*. The expected file format is:

*N*_{sites}*n**m**ε*_{1}...*ε*_{Nspecies}*σ*_{1}...*σ*_{Nspecies}*x*_{1}*y*_{1}*z*_{1}*x*_{Nsites}*y*_{Nsites}*z*_{Nsites}

where*ε*and*σ*are given for each species (*e.g.*for nanoalloys). Mie field(s) can be smoothly truncated using the optional cut-off parameter*Rc*, which will trigger the usual Stoddard and Ford procedure:*φ*(*r*) (*r*) =*φ*(*r*) -*φ*(*Rc*) - (*r*-*Rc*)*φ*'(*Rc*).*Bx*,*By*and*Bz*, which specify the periodic box dimensions.*MINBACKTCUT c*: The internal coordinate back-transformation convergence cutoff used in all cases except for interpolations. Default value is 1.0×10^{-4}*MINMAX x*: specifies the minimum value that the maximum step size is allowed to fall to. The default value is 0.01.*MLMIN in start hidden out data*: calculates probability and classification properties for*λ*min*min*neural network minima found already. Each neural network is an*MLPVB3*network (see below), and the parameters have the same meaning. The weights of each neural network should be located in a file called*MLMINweights*, which has the format:*<weight1,minimum1>**<weight2,minimum1>**<weight3,minimum1>*... *<weight1,minimum2>**<weight2,minimum2>**<weight3,minimum2>*... *MLPNORM*: Used in combination with any of the machine learning keywords. It specifies that the input features should each be rescaled by the mean of each feature. This process can help with convergence issues in machine learning. This keyword must be placed in the data file before the corresponding machine learning keyword, otherwise an error will be thrown.*MLPVB3 in start hidden out data*: specifies a perceptron neural network with one input layer of*λ**in*input nodes, one hidden layer of*hidden*hidden nodes, and one output layer of*out*output nodes.*data*is the number of data points the model trains with, stored in a file called*MLPData*. This file should be formatted as follows:*y*^{1}*x*_{1}^{1}*x*_{2}^{1}*x*_{3}^{1}... *y*^{2}*x*_{1}^{2}*x*_{2}^{2}*x*_{3}^{2}... *y*^{3}*x*_{1}^{3}*x*_{2}^{3}*x*_{3}^{3}... ... *y*^{Ndata}*x*_{1}^{Ndata}*x*_{2}^{Ndata}*x*_{3}^{Ndata}... *y*^{i}is the outcome for data point*i*, and*x*_{j}^{i}is the*j*th input feature for data point*i*. The features will be read starting from the feature in column*start*(ignoring the*y*column).The hidden and output layers also have bias weights contributing to them. The activation function for the hidden layer is hyperbolic tan. The activation function for the output layer is just the sum. Overall, the raw contribution from data point

*d*for output*i*is given by*y*_{i}^{d}(;) =*w*_{i}^{bo}+*w*_{ij}^{(1)}tanh*w*_{j}^{bh}+*w*_{jk}^{(2)}*x*_{k}^{d}(4) *p*_{i}^{d}(;) =(5) *E*(;) = - ln*p*_{c(d)}^{d}(;) +*λ*,(6) *c*(*d*) is the class label for data point*d*specified by the training set and*λ*is a constant coefficient of L2 regularisation, used to prevent overfitting. All weights are included in this L2 regularisation term, unless the keyword*NOREGBIAS*is present, in which case the bias weights are excluded from regularisation. The number of variables is*hidden×(in+out+1)+out*. The variables are ordered*w*_{jk}^{(2)}input to hidden weights (iterating over inputs first), *w*_{ij}^{(1)}hidden to output weights (iterating over hidden first), *w*_{j}^{bh}hidden bias weights, *w*_{i}^{bo}output bias weights. There are other, older keywords

*MLP3*and*MLPB3*, which were similar but had fewer weights.*MLP3*had no bias weights.*MLPB3*(now retired) was the same as*MLP3*but with a single extra bias weight added before the tanh activation function in the hidden layer. Note that*MLP3*and*MLPB3*did not have the*start*parameter available to specify, and the MLPdata file had a slightly different format: features listed before outcomes.*MLSUP in start hidden out data*: specifies a perceptron neural network similar to the*λ**MLPVB3*keyword above. The parameters all have the same meaning as above. This keyword must come after the*MLMIN*keyword in the data file. The number of inputs, start position, and number of data points must be the same as those used for*MLMIN*. The number of hidden nodes and the value of*λ*may be different. The number of output nodes must be the same as the number of neural network minima given to*MLMIN*. Each output is the softmax probability that the neural network minimum corresponding to that output is the best one to use for a given data point. In this way,*MLSUP*creates a ``neural network of neural networks": overall there is a network of weights used in a single-hidden-layered neural network, which are used to determine which neural network with weights should be used for a given data point.*MODE n1 n2*: specifies the eigenvector to be followed uphill in an eigenvector-following transition state search, where 1 means the softest mode, 2 means the next softest, and so on. Setting*n1*to 0 means that the softest mode is followed uphill at every step, otherwise a maximum overlap criterion is used to determine the mode followed after the first step. The sign of*n1*is used to determine the direction in which we step along the eigenvector if we are starting from a stationary point. This provides a way to start transition state searches from minima along any of the eigendirections in either sense. If a minimisation is started from a converged transition state then setting*n1*to ±1 enables the program to walk down the two sides of the pathway. This is true for runs based on LBFGS techniques too if the keyword*BFGSSTEP*is used.*MODE*is now also used in EF/LBFGS searches so long as an analytical Hessian is calculated.*n1*is used for the first step and*n2*for subsequent steps. The default is 0 for both parameters. Note that*n2*must be explicitly set equal to*n1*to follow the same mode (as judged by overlap) in following steps.*MODEDOWN n1 n2*: specifies an eigenvector to be followed downhill in an eigenvector-following search, where 1 means the softest mode, 2 means the next softest, and so on. This keyword is intended for use with the*INDEX*keyword and*SEARCH 2*setting. It enables us to step off a higher index saddle point and follow the corresponding mode downhill to search for a lower index saddle. If*n*2 is omitted it is set equal to*n*1 so that after the first step the downhill direction is judged by eigenvector overlap. The sign of*n*1 is used in the same way as for the*MODE*keyword to allow pushoffs in different directions along specifi modes.*MORPH morphmxstp mnbfgsmax1 mnbfgsmax2 morphemax morpherise msteps*: attempt to morph between endpoints by taking steps either towards or away from the endpoint specified in`finish`, and minimising in the tangent space.*morphmxstp*is the maximum step size.*mnbfgsmax1*is the maximum number of minimisation steps taken in the tangent space when the distance from the`finish`endpoint is greater than the step size convergence criterion.*mnbfgsmax2*is the maximum number of minimisation steps taken in the tangent space when the distance from the`finish`endpoint is less than the step size convergence criterion.*morphemax*is the maximum energy allowed during the interpolation; if this threshold is exceeded the algorithm toggles between stepping away/towards the`finish`endpoint.*morpherise*is the maximum energy rise permitted in a step.*msteps*is the maximum number of*MORPH*steps allowed. Used successfully with the general BLN model for protein L, where linear interpolation leads to strands crossing.*MSEVBPARAMS shellsToCount maxHbondLength minHbondAngle OOclash_sq*: specifies parameters for the MSEVB potential.*MULTIJOB startfile finishfile*: the same job will be rerun sequentially for input coordinates read from files*startfile*and*finishfile*. The usual coordinates are expected, for most systems after the*POINTS*keyword in`odata`, and the`finish`file, if applicable. After running this task, fresh coordinates are read from*startfile*and*finishfile*, if applicable to the run type. If the file names contain the string `xyz' then the coordinates are assumed to be in xyz format. Otherwise they are read as an uninterrupted sequence of numbers in free format.*MULTIJOB_MACHINE startfile ndof [finishfile] [i] [n] [step]*: as*multijob*but the files containing restart coordinates are unformatted non-human-readable files. Each file contains one configuration per record.*ndof*is the number of degrees of freedom in the system, i.e. the number of entries in the record.*i*and*n*are the first and last records to read from the file, respectively.*step*is the interval between consecutive record numbers which will be read. So if*i*= 2,*n*= 10 and*step*= 3, the record numbers used to run`OPTIM`jobs will be 2,5,8. Default values of the optional parameters are*NONE*(i.e. no`finish`file required), 1,`<eof>`, 1.`<eof>`means the loop will run until the end of the input files. WARNING: fortran unformatted files may not be readable on a computer other than the one where they were produced, or if your`OPTIM`executable was compiled with a different compiler to the one which produced the unformatted file.*MULTIPOT*: Use the flexible multiple potential scheme to define your system. Different atoms can interact via different types of potential and a particular atom can be associated with more than one type of potential. Detailed instructions to use this scheme are given as comments in`multipot.f90`,`pairwise_potentials.f90`and`isotropic_potentials.f90`.In theory, any subroutine with the correct signature can be used as a potential function. Only the potentials in

`pairwise_potentials.f90`and`isotropic_potentials.f90`have been tested. At the time of writing, these are the LJ, WCA and harmonic-spring potentials.`pairwise_potentials.f90`contains functions which are called for a pair of atoms at a time (e.g. harmonic springs).`isotropic_potentials.f90`contains functions which require coordinates of all the atoms involved in the interaction. Although LJ and WCA are pairwise potentials, it is more efficient to treat them as isotropic and loop over interacting pairs in the function call rather than to call pairwise_lj for every pair of atoms (*N*^{2}function calls give a large performance overhead).`pairwise_potentials.f90`and`isotropic_potentials.f90`contain generic functions for calculating the first and second derivatives of isotropic pairwise potential functions. Detailed instructions are found in the source code.An input file

`multipotconfig`is used to specify which potential functions are to be used and which atoms use each potential. For each type of potential in the system,`multipotconfig`should contain the following:*MULTIPULL npull*: allow for multiple pulled pairs of atoms to be added through the*PULL*keyword.*npull*is the number of pairs added, where a separate entry with*PULL*is needed for everyone. This keyword has to be before the first entry for*PULL*, otherwise the arrays are not correctly used.

*POT**POTTYPE n scale nparams**[params]*followed by a list of atom indices which will use this potential (the format of the list will depend on the particular potential).

*POTTYPE*is a string identifier for the type of potential being used,*n*is the number of atoms using this potential and*scale*is the energy unit for this potential (which should be set to 1.0 for at least one potential).*nparams*is the number of potential-specific parameters which are required, and*[params]*is a list of these parameters.Be aware that using

*MULTIPOT*will give a slight performance hit, because of the several function calls and bookkeeping that is associated with each call to*POTENTIAL*. This scheme is intended for playing around with composite potentials, for systems which are small enough that performance is not a big issue, or for systems involving many different potential functions which will be much too fiddly to hard-code a single subroutine.*NAB inpcrd inpcrdformat*: specifies a calculation with the interfaced version of the Nucleic Acid Builder program package. From this package the Amber force fields are being used only. The syntax is the same as for the*AMBER9*keyword. For energy and gradient evaluations the standard Amber 9 interface is being called. The NAB routines are only called for analytical second derivative evaluations. The NAB interface does not have smooth cutoffs implemented at the moment, therefore this keyword should only be used for systems where the cutoff is large.*NATB*: specifies a tight-binding potential for sodium, silver and lithium.*NATINT*: use Pulay's natural internal coordinates[29,30] wherever internal coordinates are used. These coordinates can be generated automatically or with a parameter file (using the*INTPARFILE*keyword). If using the automatically generated coordinates, the user must specify separately any rings that are not part of PRO, PHE, TYR, TRP, or HIS residues (use the*RING*keyword).*NCAP*: calls the capsid model [14], consisting of pentagonal building blocks.*NEB nsteps nimage rmsneb*: specifies a nudged elastic band pathway calculation[31,32] using a maximum of*nsteps*steps with*nimage*images and RMS convergence criterion*rmsneb*. The default values are*nsteps*=100,*nimage*=10,*rmsneb*=0.1.*NEBK nebk*: specifies the value of the force constant for NEB and DNEB runs. The default is 100, which may be larger than the optimal value for some systems.*NEBREADGUESS file*: initial images for DNEB are read from file*file*in xyz format, as dumped by*DUMPNEBXYZ*, to allow for restart from the last step, if*DUMPNEBXYZ 1*is set.*NEBREDISTRIBUTE n*: Redistribute NEB images evenly for current interpolation every*n*steps. A negative value for*n*does the initial interpolation as well, for use with*READGUESS*.*NEWCONNECT NConMax NTriesMax ImageDensity IterDensity ImageMax ImageIncr RMStol*: specifies the new connection algorithm described by Trygubenko and Wales.[18] A`finish`file containing the coordinates of a second minimum is required in the current working directory, as for*CONNECT*.*NConMax*is the maximum number of cycles allowed, default=100.*NTriesMax*is the maximum number of connection attempts for any pair of local minima in the stationary point database, default=3.*ImageDensity*is a real variable specifying the number of DNEB images to be used for the first connection attempt for any pair of minima, default=10.0. An image density is specified, so that the actual number of images is*ImageDensity*×the separation between the two minima. If*NTriesMax*> 1 then the image density is increased by*ImageIncr*for each attempt, up to a maximum of*ImageMax*images in total. The default values for*ImageIncr*and*ImageMax*are 0.5 and 400, respectively.*IterDensity*specifies the maximum number of iterations used to optimise the DNEB in terms of a density. The actual value used is*IterDensity*×the number of images. The default value of*IterDensity*is 30.0.*RMStol*is the convergence condition for the RMS DNEB force on all the images. See also*DNEBEFRAC*.*NEWCONNECT*runs can be restarted and continued using the*REDOPATHXYZ*keyword. All`path.n.xyz`files numbered sequentially from 1 will be read, along with a`pairs.newconnect`file (optional) to provide the history of connection attempts. Make sure the number of NEWCONNECT cycles is large enough to read all the`path.n.xyz`files and continue as required.*NEWNEB Nimage NIterMax RMSTol*: specifies that the DNEB algorithm[18] should be used for a double-ended transition state search.*Nimage*,*NIterMax*and*RMSTol*are the number of images, the maximum number of iterations and the RMS force convergence condition, respectively. The default value for*Nimage*is 2 and there are no defaults for the other parameters. If*NEWCONNECT*is also specified then these values are used for the first*NEWCONNECT*cycle only. However, if*CONNECT*is specified they are used for every cycle. See also*DNEBEFRAC*.*NGUESS n*:*n*is the number of transition state guesses to be tried in**guessts**for CHARMM or UNRES before switching back to*NEB*or*NEWNEB*.*NOCHIRALCHECKS*: disables checks for inversion of CA atoms and chiral side-chains for ILE and THR.*NOCISTRANS minomega*: used in*CONNECT*and*NEWCONNECT*runs to reject transition states that connect two minima with different omega angles, i.e. to prevent cis-trans peptide isomerisation. Checks that all residues besides proline are in the trans state and rejects transition states and minima that are not, i.e. with |*ω*| <*minomega*.*minomega*defaults to 150 degrees. For proline every*ω*is allowed. NOCISTRANS is the default for CHARMM, AMBER9 and NAB, i.e., no need to specify this line in the*odata*file unless you want to change*minomega*. If you want to allow for cis-trans isomerisation, you have to specify the CISTRANS keyword.*NOCUDALBFGS*: do not use the CUDA LBFGS routine. If*CUDA A*is present, the wrapper for AMBER CUDA energy and gradient will still be used, and the CPU version of LBFGS. This setup enables other terms to be added to the potential, e.g. using the*PULL*keyword.*NOFRQS*: specifies that frequencies are not present in`path.info`files. Used for very large systems where frequency calculations are not feasible in conjunction with the same PATHSAMPLE keyword.*NOHESS*: no Hessian should be calculated during geometry optimisation. Hybrid EF/LBFGS transition state searches are therefore conducted without a Hessian. The smallest eigenvalue and the corresponding eigenvector are found from a separate Rayleigh-Ritz minimisation problem for every combined EF/BFGS step.*NOINTNEWT*: when doing the back transformation from internal to Cartesian coordinates, solve the linear problem only. Do not do the Newton's-method iterations. This was the default in previous versions of OPTIM.*NOINVERSION*: turns off inversion of structures for distance metric in**minpermdist**.*NOIT*: for use with hybrid eigenvector-following runs when a Hessian is available. Specifies that the required lowest eigenvalue and eigenvector be found using LAPACK routine**DSYEVR**instead of by iteration.*NOLBFGS*: For the growing string or evolving string double-ended transition state search methods, instead of using L-BFGS optimisation to evolve the strings, simply take steps in the direction of the perpendicular force.*NONEBMIND*: do not put end point structures supplied to DNEB into closest coincidence.*NONLOCAL x y z*: factors for averaged Gaussian, Morse type 1 and Morse type 2 potentials.*NOPOINTS*: printing of coordinates to file`points`for intermediate steps is turned off. The default is true.*NORANDOM randomcutoff*: used in CHARMM transition state guessing procedure together with*TWISTTYPE*. Setting*randomcutoff*very large prevents random steps, and is recommended.*NORESET*: specifies that periodic images should not be returned to the primary supercell for calculations involving periodic boundary conditions. (May be useful for calculating transport properties with kinetic Monte Carlo).*NOTE*: has the same effect as*COMMENT*, i.e. the rest of the line is ignored.*NOTRANSROT*: forbid overall translation/rotation in alignment and distance calculations.*NTIP 4*: calls the TIP4P model of water molecules.*ODIHE*: for use with*CHARMM*. Specifies calculation of a dihedral-angle order parameter using the reference structure supplied in`ref.crd`.*OH*: add an octahedral field of strength*x*to the potential.*OHCELL*: allow point group operations for a cubic supercell in subroutine`minpermdist.f90`permutational distance minimisation.*ONETEP job system*: tells the program to use a`ONETEP`executable to calculate energies and forces with input files based on the system name*system*. Periodic boundary conditions are not assumed, so projection or shifting is performed to remove overall translation and rotation.*job*is a string in quotes that specifies the system call required to run the`ONETEP`executable. The line `print_qc : TRUE' is needed in the`system.dat`file so that the total energy is printed in a form that`OPTIM`can grep for. OPTIM will change the line with `read_denskern' in the`system.dat`file to TRUE after the first call to obtain the ONETEP energy and gradient. This saves a great deal of cpu time in subsequent CASTEP steps. However, it means that the final dat file is altered, and you will need to change read_denskern to FALSE to restart the job if a valid`system.dkn`file is not present in the working directory. ONETEP will fail and stop if the wavefunction read fails. Note that you may not be able to restart a job with a different number of nodes using a saved density (not tested). The*PARALLEL*keyword is not needed, since the number of processors can be specified in*job*if necessary. Example for volkhan:ONETEP 'mpirun /home/wales/bin/onetep' 'ethene'

For a

*CASTEP*or*ONETEP*normal mode analysis set*STEPS 0*,*MASS*,*ENDHESS*, and*ENDNUMHESS*in`odata`. The Hessian eigenvalues and normal mode frequencies are printed to standard output automatically. Check`pertable.f`first to make sure that the atomic mass is known for all the elements in your system. The frequency conversion assumes that the units of energy and distance are electron volts and Å. If*DUMPVECTOR ALLVECTORS*is set in`odata`then all the normal mode eigenvector components will be transformed to the Cartesian basis from the mass-weighted Cartesian basis.*OPEPHIRE option start*: alternative use*OPEP*or*HIRE*, specifies the use of the HiRE and OPEP potentials,*option*is Protein, RNA, DNA, MixedRNA or MixedDNA. The following additional files are needed for OPEP protein simulations: conf_initiale.pdb, ichain.dat, scale.dat, cutoffs.dat, parametres.top and parametres.list. For RNA and DNA simulations the following files are required: conf_initiale.pdb, conf_initiale_RNA.pdb, ichain.dat, scale_RNA.dat, cutoffs_RNA.dat, parametres_RNA.top, baselist.dat, bblist.dat, chargeatm_RNA.dat and protonated.dat. Coordinates for the potential are provided by start and finish.*OPTIMIZETS*: optimise transition states at the end of each DNEB run. Default false. Set to true by*NEWCONNECT*.*ORBITGEOMTOL x*: sets the cutoff value for assigning atoms to the same orbit when analysing the standard orientation in routine**myorient**. The default value for*x*is 0.3. If*x*is too small it is possible for permutational isomers to be missed.*ORT*: remove overall rotation and translation for DNEB runs. Default false.*OSASA rpro*: for use with*CHARMM*. Specifies calculation of a solvent accessible surface area order parameter using probe radius*rpro*.*PAHA n*: calls a finite system of polycyclic aromatic hydrocarbons (PAH) interacting via a general anisotropic potential developed from first principles [33]. The PAH ID*n*defines the PAH molecule: 1 for benzene, 2 for naphthalene, 3 for anthracene, and 4 for pyrene.*PAP npatch alpha s cosdel epsilon*: specifies a patch anti-patch potential. Each body consists of a Lennard-Jones core, range parameter*alpha*, with*npatch*patches and*npatch*anti-patches. The patch anti-patch attraction has a range specified by*s*, a width specified by*cosdel*and a strength specified by*epsilon*. If*npatch*is set to zero, site information will be read in from the file`papsites.xyz`.*PARALLEL nproc*: specifies that auxiliary programs such as`GAMESS`and`CPMD`use*nproc*processors. Not required for`CASTEP`.*PARAMS*: enables additional parameters to be set for specific potentials, e.g.*Z*^{*}for LJAT,*ρ*_{0}for Morse,*n*,*m*, the box lengths*L*_{x},*L*_{y}and*L*_{z}and the cutoff for ME, the box lengths*L*_{x},*L*_{y}and*L*_{z}and the cutoff for JM, SC and P6, and*ε*,*c*and*σ*for Au, Ag and Ni. Note that all the numbers are read as real.*PATH n de ds*: requests calculation of the pathway connecting two minima from the transition state specified in odata.*n*is the number of intermediate points files to save on either side, default*n*=3. To choose which frames are dumped in the`path.xyz`file a stochastic method is employed. All three stationary points are always included. Other frames are dumped with a probability proportional to*n*. If*n*exceeds the number of frames in the path then they will all be dumped, up to a maximum of 100. This behaviour can be modified by specifying the optional parameters*de*and*ds*. These are thresholds for the energy change and path length change required for the next frame to be included. The defaults are both zero. The complete xyz file is printed to`path.xyz`and the energy as a function of path length is printed to file`EofS`. A summary of the path characteristics such as barrier heights, path lengths and cooperativity indices is printed at the end. If*READVEC*is present in`odata`then the required eigenvector corresponding to the displacement direction will be read from`vector.dump`, otherwise it will be calculated by diagonalizing a Hessian (for*SEARCH 2*) or using an iterative approach (for*BFGSTS*with or without*NOHESS*;*NOIT*can also be used with*BFGSTS*.) After the initial step the energy will be minimised by whichever first or second order method is specified in`odata`, i.e. eigenvector-following or second-order Page-McIver for*SEARCH 0*and 6 and 7, LBFGS for*BFGSMIN*, and first order steepest-descent for*BSMIN*and*RKMIN*. A hybrid method can be specified using*HYBRIDMIN*. See also*DUMPPATH*and*PATHSDSTEPS.*.*PATHSDSTEPS n*: specifies the maximum number of minimisation steps in a pathway calculation before switching to LBFGS. Can be used with search types*PBS*: for use with*MCPATH2*; distribute sampling for independent blocks over as many cores as specfied by the`qsub`script for PBS.*PERMDIST x nsec*: minimise distances between stationary points with respect to permutational isomerisation. Requires the auxiliary file`perm.allow`to specify permutable atoms, otherwise all atoms are assumed to be permutable. The absence of a`perm.allow`file is considered a mistake for*CHARMM*runs.The first line of the

`perm.allow`file must contain an integer that specifies the number of primary groups of interchangeable atoms. The groups then follow, each one introduced by a line with two integers*p*and*s*that specify the number of permutable atoms in the primary group and the number of other sets of permutable atoms associated with the primary set. When a permutation is applied to the primary set, the same permutation is applied to the atoms in the secondary set. The secondary sets must all be the same size as the primary set, i.e.*p*members.*s*may be zero; this is the usual case. The following line contains the indices of the*p*permutable atoms in the primary set and then the indices of the atoms in each of the*s*secondary sets, one set at a time.The parameter

*x*is the distance tolerance for assigning atoms to orbits in the**myorient**standard orientation routine, default value 0.3. If*x*is too small it is possible for permutational isomers to be missed. The parameter*nsec*specifies the maximum number of atoms permitted in secondary sets. The default is 3, which is sufficient for methyl groups in bio-molecules. Rigid bodies may require a higher number.For the phenylalanine example illustrated above we must allow three other pairs of atoms to exchange if we swap 7 and 8. Hence a suitable

`perm.allow`entry is1

2 3

7 8 5 6 1 2 3 4

This should be on three consecutive lines. Here

*n*= 2 and*s*= 3: if we exchange 7 and 8 then we must also exchange 5 and 6, 1 and 2, and 3 and 4. There are two atoms in each of the three secondary sets, since we have specified 7 and 8 as the two primary atoms.Here is an example

`perm.allow`file for a water trimer using the flexible*QTIP4PF*potential, where the energy is invariant to permutations of water molecules and to exchanges of hydrogens in the same molecule. However, hydrogens cannot exchange between different oxygens:4

3 2

1 4 7 2 5 8 3 6 9

2 0

2 3

2 0

5 6

2 0

8 9

The first group of three oxygens has two atoms that must move with each oxygen, i.e. atoms 2 and 3 for oxygen 1, etc. Hydrogen permutations for each oxygen are allowed by the three following groups. This scheme allows atoms to appear in more than one group. There must be a group containing each complete set of permutations in order for permutation-inversion isomers to be recognised. The format is compatible with an older scheme, where only pair swaps were allowed for associated atoms, but now allows for more general permutations.

Scripts to generate allowed permutations automatically for CHARMM and AMBER are available from the group web site. It is essential to use symmetrised versions of the corresponding force fields!

*PERMDISTINIT x*: performs the permutational analysis described above for*PERMDIST*, but only for the initial alignment of two end points. After this is done, the permutational optimisation is turned off, which can save time.*PERTDIHE chpmax chnmin chnmax iseed*: CHARMM and UNRES dihedral angle perturbation specification. Performs random,`GMIN`-style twists before starting optimisation.*POINTS*: this is usually the last keyword and introduces the coordinate information, which is read one atom per line. Each line must consist of the atomic symbol of the atom followed by its three Cartesian coordinates. Leading spaces before the atomic symbol should be avoided. For calculations involving CHARMM, UNRES, AMBER and CPMD the coordinates are obtained from auxiliary files, and*POINTS*will be the last OPTIM directive in the`odata`file, or is not used (CHARMM and UNRES).*PMPATH inr*: calculates the approximate steepest-descent pathways leading from a transition state with the Page-McIver second order formulation.*inr*can be 6 or 7, and has the same effect as the corresponding settings for the*SEARCH*keyword.*inr*=6 should only converge to minima (default), while*inr*=7 produces paths that can terminate at saddle points.*PREROTATE*: For the GS and ES double-ended transition state search methods, if using*FIXATMS*to zero some coordinates of the forces to avoid overall translation and rotation, this keyword will rotate the start and end points so that those coordinates are zero in both. The default is true.*PRESSURE*: if present tells the program to perform a constant zero pressure optimisation for bulk SC, ME, MP, MS and P6. Normally a constant volume optimisation takes place.*PRINT n*: sets the print level. The default value is zero. Use of this option is not recommended, since more specific print control is possible.*PRINTCOEFFICIENTS*: prints ground state coefficients for the MSEVB potential.*PTSTST npatch eps cosdel kappa*Specifies a patchy site-to-site potential, similar to*PAP*but with Gaussian patches on the surface of the particle. The number of patches is determined by*npatch*.*eps*is the strength of the Gaussian patch attraction and*cosdel*is the effective range of the Gaussian.*PULL a1 a2 f*: apply a static force to the potential, equivalent to adding the term*V*_{pull}= -*f*(*z*_{a1}-*z*_{a2}). Here*z*_{a1}and*z*_{a2}are the*z*coordinates for atoms*a*1 and*a*2, and*f*specifies the force. This potential is designed to simulate a pulling experiment with static force where a molecule is pulled along the*z*axis from atoms*a*1 and*a*2.*PUSHCUT x*: sets the threshold for the RMS force below which the system may apply a*PUSHOFF*to escape from a stationary point of the wrong Hessian index. Default value is 0.00001. Using a negative value prevents pushoffs from occurring.*PUSHOFF x*: sets the magnitude of a step away from a stationary point of the wrong Hessian index (see §8 for default action). Default value is 0.01. Formally used as the step size in hybrid eigenvector-following transition state searches if the eigenvalue of the direction being followed is positive.*MAXMAX*has now replaced*PUSHOFF*in this role.*PUSHOPT x conv max*: specifies that the magnitude of steps away from a transition state in path calculations should be calculated using a golden section search in the interval [0 :*x*] and [0 : -*x*] for the tw directions. The search terminates when the pushoff magnitude for the lowest energy in the line search is identified to an accuracy of*conv*, or when*max*iterations have been performed.*PV press gtol grad steps*: specifies an approximate constant pressure optimisation with pressure*press*and convergence criterion*gtol*for the gradients with respect to the box lengths. If any box length gradient is larger in magnitude than*grad*then up to a maximum of*steps*optimisation steps for the box lengths are performed. If the three box lengths are equal to start with and the keyword*CUBIC*is included, then a cubic box is maintained. Will not work with atom types MP, ME and MS. Default values,*press*=0,*gtol*=0.001,*grad*= 10^{60},*steps*=100.*PVTS press gtol grad nboxts*: as for*PV*but searches for a transition state with respect to box length*nboxts*, where*nboxts*=1, 2 and 3 specify the*x*,*y*and*z*box lengths, respectively.*nboxts*defaults to 1.*PYG a1 a2 a3 b1 b2 b3 sigma0 eps0*: calls a finite system of Paramonov-Yaliraki ellipsoids [34], where the potential involves a set of eight parameters, six of them, {*a*_{k}} and {*b*_{k}} (*k*= 1, 2, 3), defining two different shape matrices for the repulsive and attractive parts of the interaction in terms of the lengths of the semi-axes, and the other two,*σ*_{0}and*ε*_{0}, defining the length and energy scales, respectively.*QCHEM qchemjob sys*: calculate energy and gradient using the`QCHEM`program.*qchemjob*is a string specifying how to run the`QCHEM`executable, and*sys*is a string specifying the`QCHEM`input file.*QCHEMSCF qchemjob sys nao nmo nalpha nbeta*: specifies a`QCHEM`job to search the SCF solution landscape.*qchemjob*is a string specifying how to run the`QCHEM`executable, as for conventional geometry optimisation, and*sys*is a string specifying the`QCHEM`input file.`nao nmo nalpha nbeta`are the number of atomic orbitals, molecular orbitals, alpha spin, and beta spin electrons, respectively. The initial molecular orbital coefficients are read from the file`start`. The output file`qcoverlap`is needed in the current working directory for`PATHSAMPLE`to calculate distance metrics between solutions. An example job for the H_{4}molecule with a 3-21G basis could have

QCHEMSCF 'qchem -save -nt 1' 'h4' 8 8 2 2

and a`QCHEM`input file`h4`containing $comment H4 HF 3-21G Single point energy $end$molecule 0 1 H 1.00000 1.000000 0.00000 H 1.00000 -1.000000 0.00000 H -1.00000 -1.000000 0.00000 H -1.00000 1.000000 0.00000 $end

$rem method hf Exact exchange BASIS 3-21G Basis Set SCF_CONVERGENCE 8 Tight convergence sym_ignore true unrestricted true SYMMETRY FALSE SCF_MAX_CYCLES 0 GEN_SCFMAN TRUE SCF_GUESS READ $end This system has 128 molecular orbital coefficients but only 24 variables. Note that

`QCHEM`performs zero SCF cycles because we seek the energy for a given set of molecular orbital coefficients, and derivatives with respect to the degrees of freedom specified by a constraint surface (Thouless transformation). With BASIS aug-cc-pVDZ the`odata`line is

QCHEMSCF 'qchem -save -nt 1' 'h4' 36 36 2 2

and there are 2592 molecular orbital coefficients and 68 variables.*QCHEMGHF qchemjob sys nao nmo nelec*: specifies a`QCHEM`job to search the SCF solution landscape for the GHF approach.*qchemjob*is a string specifying how to run the`QCHEM`executable, as for conventional geometry optimisation, and*sys*is a string specifying the`QCHEM`input file.`nao nmo nelec`are the number of atomic orbitals, molecular orbitals, and electrons, respectively. The initial molecular orbital coefficients are read from the file`start`. The output file`qcoverlap`is needed in the current working directory for`PATHSAMPLE`to calculate distance metrics between solutions. An example job for the H_{4}molecule with a 3-21G basis could have

QCHEMSCF 'qchem -save -nt 1' 'h4' 8 8 4

and a`QCHEM`input file`h4`containing $comment H4 HF 3-21G Single point energy $end$molecule 0 1 H 1.00000 1.000000 0.00000 H 1.00000 -1.000000 0.00000 H -1.00000 -1.000000 0.00000 H -1.00000 1.000000 0.00000 $end

$rem method hf Exact exchange BASIS 3-21G Basis Set SCF_CONVERGENCE 8 Tight convergence sym_ignore true unrestricted true SYMMETRY FALSE SCF_MAX_CYCLES 0 SCF_GUESS READ GEN_SCFMAN TRUE SCF_SAVE_HESSIAN TRUE $end Note that, as for

*QCHEMSCF*,`QCHEM`performs zero SCF cycles because we seek the energy for a given set of molecular orbital coefficients, and derivatives with respect to the degrees of freedom specified by a constraint surface (Thouless transformation). This system has 256 molecular orbital coefficients but only 48 variables.*QCI or INTCONSTRAINT intconstrainttol intconstraintdel intconstraintrep intconstrainrepcut intconfrac intconsep intrepsep intsteps1 intconsteps intrelsteps maxcone intgradtol*specifies quasi-continuous interpolation via an auxiliary constraint potential.*intconstrainttol*is used to determine constrained distances. The deviation of the distance between a given pair of atoms in all reference structures from the average must be less than*intconstrainttol*, default 0.1, for this separation to constitute a constraint. If a percolating network of constraints does not result then*intconstrainttol*is increased by 10% and the analysis repeated. This parameter is not used if*QCIAMBER*is set, since the bond length and angle constraints are set automatically, and additional planarity constraints can be read from the file`constraintfile`. This file can be generated using the program`aaextraconstraint.f90`located in the`svnSCRIPTSOPTIM`directory, which requires a pdb file called`coords.inpcrd.pdb`in the current working directory. The list of backbone atoms for keyword*DOBACKALL*is also generated in file`aabk`by the`aaextraconstraint.f90`program.*intconstraintdel*multiplies the constraint penalty term in the auxiliary potential, default 1.0.*intconstraintrep*multiplies the repulsive penalty term in the auxiliary potential, default 1.0. A dimensionless form of the penalty function is now used, so these factors only have an effect if they are set to zero to ignore one set of terms.*intconstrainrepcut*is the cutoff for the repulsive penalty term in the auxiliary potential, default 1.7.*intconfrac*is the fraction of the true potential used for the second optimisation phase after the interpolation with the constraint potential has been achieved. The default value is 0.9.*intconsep*is the maximum difference between the order number of atoms for which constraints are allowed. The default is 15, which seems appropriate for biomolecules. However, if a`congeom`file of reference minima is specified, or a corresponding`congeom.dat`file is present, or if*QCIAMBER*is set, then*intconsep*can be set greater than the total number of atoms.*intrepsep*is the minimum difference in order number of atoms for which repulsive terms are added to the potential. The default is zero; there are no repulsive terms between constrained atoms.*intsteps1*is the maximum number of minimisation steps allowed for optimisation of the interpolation potential, default 300000.*intconsteps*is the number of additional minimisation steps after interpolation with the auxiliary potential has been achieved, where the potential is changed to include a fraction*intconfrac*of the true potential, default 100.*intrelsteps*is the number of minimisation steps allowed after adding an atom in the interpolation phase before a new atom is added, even if the convergence conditions on the interpolation metric and root mean gradient have not been achieved, default 200. In the current setup if*QCIRESET*is used then a much larger value may be better so that atoms are not added until a convergence condition is hit.*maxcone*is the convergence threshold for the highest value of the auxiliary constraint or repulsive potential for a single atom, default 0.01.*intgradtol*is the convergence threshold for the highest absolute value of the auxiliary constraint or repulsive potential for a single atom, default 0.01.Any number of reference minima can be specified in the additional file

`congeom`in the current working directory. If this file is found then the constraints and repulsive terms are fixed using these minima, and a summary of all the terms required for the interpolation potential is written to file`congeom.dat`. If neither file is found then the interpolation potential is based on the two end points only, unless*QCIAMBER*is employed with a separate`constraintfile`, which is strongly recommended. and it may be necessary to set*intconsep*. All geometries are permutationally aligned in defining the interpolation potential, using e.g.*PERMDIST*or*LOPERMDIST*. When`congeom`or`congeom.dat`is used all minima are permutationally aligned to the first minimum in the reference set. See also*CONINT*,*CONCUTABS*,*CHECKREP*,*INTFREEZE*,*INTIMAGE*,*INTSPRINGACTIVE*,*KINT*,*MAXCON*,*QCIADDACID*,*QCIADJUSTK*,*QCICONCUT*,*QCIIMAGE*,*QCIIMAGEDENS*,*QCICYCLES*,*QCIDOBACKALL*,*QCILPDCON*,*QCILPERMDIST*,*QCIMAXACTIVE*,*QCIRESET*,*QCISTOP*,*QCITRILAT*.*QCIADDACID*: specifies that the QCI routine should add atoms for each amino acid residue in turn, until it hits one with fewer than three active constraints. Atoms are added individually as normal once a pass through all residues has been completed. This option is not recommended.*QCIALIGN*: species a list of atoms for the initial end point alignment of end point minima. The list is read from file`QCIalign`, where the first line must contain the number of entries to be read.*QCILINEAR*: species a list of atoms that should have linear interpolation applied from the start of the QCI procedure. The list is read from file`QCIlinear`, where the first line must contain the number of entries to be read.*QCIDOBACKALL*: specifies that the QCI routine should add all backbone atoms for each amino acid in turn, including the atoms connected to the C_{α}carbon. Atoms are added individually as normal once a pass through all residues has been completed. The backbone atom file`aabk`is required in the current working directory, generated by`aaextraconstraint.f90`(located in the`svnSCRIPTSOPTIM`directory).*QCIFREEZE or INTFREEZE x*specifies the root mean square force on a QCI interpolation image below which it is frozen when*INTCONSTRAINT*is used. The default value for*x*is 0.001.*QCIRESET qciresetint*: if the number of QCI steps exceeds*qciresetint*since the last atom was added, or since the last spring constant reset, or the last change in a permutational group or chiral inversion, then slacken the convergence criteria. Either or both of the*QCI*convergence parameters is increased by 5%, depending on which appear to be too tight.*KINT kint*: spring constant for springs between QCI images. Default zero. See also*QCIADJUSTK*.*QCIADJUSTK qciadjustjfrq qciadjustktol qciadjustkfrac qcikintmin qcikintmax*: increase or decrease the QCI spring constant*KINT*every*qciadjustjfrq*(default 0, no adjustment) steps by a factor of*qciadjustkfrac*(default 1.05) according to whether the percentage distance deviation of the images from the mean spacing is greater or less than qciadjustktol (default 10.0), respectively. The last two parameters specify lower and uppoer bounds on the spring constant, default 0.01 and 100. This keyword is analogous to*ADJUSTK*for the DNEB procedure.*QCILPERMDIST qcipdint qcipermcut*: for QCI interpolations, check the permutational alignment using the local permdist routine at intervals of*qcipdint*with alignment tolerance of*qcipermcut*. Atoms are permuted if the alignment agrees for the two fixed end points. This approach is the same as the normal local permutational alignment scheme, but applied to one permutational group at a time. The cutoff for accepting new atoms into the environment may need to be larger than usual, because QCI images may have more distorted geometries.*QCILPDCON qcipdint*: for QCI interpolations, check the permutational alignment using the local permdist routine based on all active atoms constrained to all the atoms of the permutational group at intervals of*qcipdint*. Atoms are permuted if the alignment agrees for the two fixed end points. For some groups, such as NH_{3}^{+}in LYS and NH_{2}is ASP, there is axial symmetry, and alignment may be ambiguous. In this case we take the permutation with the fewest atom moves for alignments within GEOMDIFFTOL.*INTSPRINGACTIVE*: for QCI procedure, only apply spring terms for active atoms. Default*QCIMAXACTIVE imaxnactive*: for QCI interpolations, only allow*imaxnactive*active atoms. The active atoms drop off the list according to when they were first added. Probably best not to use this feature, so set*imaxnactive*greater than the number of atoms.*QCICYCLES qcicycdist qcicycn*: for QCI interpolations, only use QCI for gaps larger than*qcicycdist*and for cycles up to*qcicycn**QCICONCUT intconcut*: for QCI interpolations, don't allow constraints between atoms separated by more than*intconcut*in either endpoint, default 100.0.*INTCONCUT*is the same.*QCIIMAGE or INTIMAGE imsepmin imsepmax intimage maxintimage intntriesmax intimageincr intimagecheck*specifies the behaviour of interpolation images for the*INTCONSTRAINT*quasi-continuous interpolation procedure.*intimagecheck*(default 25) is the interval for checking the spacing of the interpolation images. Images separated by less than*imsepmin*(default 0.2) can be combined, while an additional image can be added between images further than*imsepmax*(default 10.0) apart.*intimage*is the initial number of images (default 3),*maxintimage*is the maximum number of images (default 75),*intntriesmax*is the maximum number of quasi-continuous interpolation attempts for a given pair of minima (default 2), and*intimageincr*(default 6) is the increment in the number of initial images for further connection attempts between minima that have already been tried. It may be better to use*QCIIMAGEDENS*, documented below.*QCIIMAGEDENS density max*: use a fixed number of QCI images determined as the end point distance times the*density*parameter, with a maximum number of images*max*.*QTIP4PF*: flexible water potential from Habershon*et al.*[*J. Chem. Phys.*,**131**, 024501 (2009)] coded by Dr Javier Hernández-Rojas. The units of length and energy are Å and kcal/mol. The atoms must be entered in the order O, H, H, O, H, H, etc.*QSPCFW*: flexible water potential from Paesani*et al.*[*J. Chem. Phys.*,**125**, 184507 (2006)] coded by Dr Javier Hernández-Rojas. The units of length and energy are Å and kcal/mol. The atoms must be entered in the order O, H, H, O, H, H, etc.*QUIPZ z*: define the atomic number*z*for the quip interface.*QUIPLATT matrix*: defines the components of a 3×3 lattice for the quip interface.*QUIP_PARAM_FILE qpf*: sets the quip parameters file.*qpf*is a string and the default is quip_params.xml.*QUIP_INIT_ARGS_STR ias*: sets the quip parameter `init_args_str'.*ias*is a string with default value `xml_label=default'.*RADIUS x*: specifies that atoms should not be allowed to move beyond a distance*x*from the origin.*RANROT n*: for use with*PERMDIST*. Specifies that*n*random orientations will be tried as well as the initial standard alignment in`minpermdist.f90`. Several hundred random orientations may be needed to find the best translational/rotational/permutational alignment of end points.*RANSEED n*: specifies the initial seed for random number generation, as used in hard sphere moves with*FIXD*.*RATIOS*: specifies that the pathway parameters needed to calculate catastrophe ratios should be printed in a*PATH*run.*RBSYM*: specifies that internal symmetry operations permuting equivalent sites for rigid-body building blocks exist. The operations are read in from a file`rbsymops`, which must exist in the working directory. The first line of the file is an integer that specifies the number of operations generated by proper axes of rotation including the identity operation; the operations are then read in one at a time in a representation consisting of a unit vector, defining the axis in the reference frame, and an angle in degrees, describing the magnitude of rotation about that axis. The first operation has to correspond to the identity operation.This keyword has to be combined with

*PERMDIST*so that structures are aligned and a distance metric considered based on permutations of identical rigid bodies and any internal symmetry operation of each rigid body that is a symmetry of the potential energy function.*READMASS*: atomic masses will be read from file`masses`in the current working directory. This option may be useful for normal mode analysis with potentials such as binary Gupta.*READPATH*: if specified with*CALCRATES*then rate constants will be calculated for the transition states found in`path.info`and no stationary point searches will be performed.*READSP*: instructs`OPTIM`to read minima and transition state data in the PATHSAMPLE format. This has not been implemented yet!*READHESS*: Hessian will be read from file`derivs`at first step.*READVEC*: if present the Hessian eigenvector corresponding to the smallest eigenvalue will be read from file`vector.dump`. The latter file can be generated using the*DUMPVECTOR*keyword in a previous run.*NEWREAXFF*: specifies the use of the REAXFF force field. The following additional files are needed: fort.3 or start, which contain the starting geometry, fort.4, which contains a specific force field parametrization, control, which contains additional force field settings. We recommend using ReaxFF with a start file for the coordinates, in which case fort.3 will only be used to read atomic symbols and number of atoms in the system. The format of fort.3 is BGF and is format-sensitive.*REAXFFDECOMP*: print energy decomposition file (fort.200) for REAXFF.*REDOPATH*: instructs`OPTIM`to read transition state coordinates successively from the file`redopoints`during a*NEWCONNECT*run. Can be used to generate movie files from stationary point sequences calculated by PATHSAMPLE. The correct start and finish coordinates for the minima must be present in the`odata`and`finish`files. The`odata`file should contain a*PATH*keyword with sufficeint frames to make a movie. Just using*PATH*with no arguments will just dump the three stationary points in each case, which were already known from the input. The number of*NEWCONNECT*cycles must be greater than the number of transition states in the path.There can often be problems for long paths if a transition state does not manage to match the two minima in the dicrete path that has been read in.

`OPTIM`will try different parameters for the path run in this case, and will continue to try and bridge any gaps that remain when the`pathdata`file is exhausted, if there are additional*NEWCONNECT*cycles available.Each transition state should already be converged, and the transition state searches should converge immediately. However, in a gradient-only

*BFGSTS*run, the initial eigenvector guess is random to begin with, so more Rayleigh-Ritz steps may be needed. It is a good idea to increase this maximum value on the*BFGSTS*line.*REDOPATHXYZ*: as for*REDOPATH*above, except that existing`path.n.xyz`files are read instead of actually calculating pathways for the transition states.*NEWCONNECT*runs can be restarted and continued using the*REDOPATHXYZ*keyword. All`path.n.xyz`files numbered sequentially from 1 will be read, along with a`pairs.newconnect`file (optional) to provide the history of connection attempts. Make sure the number of NEWCONNECT cycles is large enough to read all the`path.n.xyz`files and continue as required.*REDOTS n*: The CONNECT algorithms often find the same refined TS multiple times. This keyword specifies that the first*n*times a TS is found, the pushoff path is calculated as normal. Subsequent times that the TS is found, the path is not calculated and the TS simply ignored.*n*has default value 2 (i.e. one re-try of the path run).*REDUCEDBONDLENGTH blfactor CB*: rescales the bond lengths by a factor of*blfactor*in the side chains of proteins, if modelled by one of the CHARMM potentials.*blfactor*has to be specified, and its default value is one.*CB*is an optional argument. When set, the bond length between the C_{α}and C_{β}atoms is rescaled by*blfactor*as well, otherwise not.*REOPT*: specifies that the eigenvector to be followed should be reoptimised in a BFGSTS search after the EF step and before the tangent space minimisation. This is probably not a good idea. Default is false.*REOPTIMISEENDPOINTS*: specifies that endpoint minima should be reoptimised if their RMS force lies above the convergence threshold. Useful in connection runs where failure is guaranteed if one or more of the endpoints is not identified as a minimum. A large RMS force at the beginning of a connection run driven by PATHSAMPLE should be investigated because it suggests a problem, e.g. with*CHARMM*permutational isomerisations. Default is false.*REPELTS*: specifies that the transition state search direction should be orthogonalised to the coordinates in file`points.repel`.*RESIZE x*: scales all the coordinates by*x*before the first step is taken.*REVERSEGEDIFFTOL*: Reverses the order of comparison between two structures (minima and transition states). First, their cartesian distance will be calculated and compared. If the distance is larger than GEOMDIFFTOL, the structures are different. If the distance is less than GEOMDIFFTOL, the energies of the two structures will be compared. If their energies differ by more than EDIFFTOL, the structures are considered different, or else identical. Typically, this leads to a slower calculation since the energies are already present, while the distance comparison requires additional calculation. Nevertheless, this is useful in cases where the energy landscape is noisy and has a very rough topography (i.e. structuraly very similar structures), which is sometimes the case for ReaxFF force fields. When using this keyword, it is also important to use MAXIMFACTOR in order to properly scale the factor used to identify local maxima for hybrid EF TS searches (It multiplies EDIFFTOL).*RIGIDINIT AACONVERGENCE*: This will turn on the local rigid body framework. This keyword needs two additional input files:*coordsinirigid*and*rbodyconfig*.*coordsinirigid*should contain the coordinates of all the atoms whether they are part of local rigid bodies or not. During initialization, OPTIM will select appropriate coordinates and throw away irrelevant ones. The format is:*x1 y1 z1**x2 y2 z2**ldots**ldots**xn yn zn*

The file

*rbodyconfig*defines the rigid bodies, with the following format:*GROUP NoAtomsInGroup**Atom 1**Atom 2**ldots**ldots**Atom N*

This keyword takes an optional argument

*AACONVERGENCE*. If present, this switches on the use of the more accurate distance measure and method of calculating the RMS force for angle-axis coordinates described in this paper: V. Ruhle, H. Kusumaatmaja, D. Chakrabarti and D. J. Wales,*J. Chem. Theory Comput.*, 2013,**9**, 4026-4034.*RIGIDMOLECULES*: For use only in conjunction with*RIGIDINIT*. Indicates a system composed of multiple rigid bodies and having no free atoms. This is a temporary keyword, used to isolate some parts of the rigid body code from the biomolecule potentials and similar. Most users probably don't need to use it, but talk to sn402 if you're unsure. Hopefully this keyword will soon be removed completely and its functionality absorbed into other keywords as appropriate.*RING a1 a2...*: When using natural internal coordinates, specifies a ring that's not part of a PRO, PHE, TYR, TRP, or HIS residue.*a1, a2*, etc. are the atom numbers for the ring in consecutive order. Only rings of size 5 or 6 are permitted.*RINGPOLYMER rpsyst nrp rpbeta rptype*: Specifies a ring polymer system with harmonic springs between nrp images of the same system that generally have different geometries. rpsyst is a string specifying the system: AECK (asymmetric Eckart barrier), SD (Stillinger-David flexible water potential), TT (Xantheas' TTM3-F water), MCY (VRT(MCY-5f) water), JB (James Bowman's water), MB (MBPol water).

nrp is the number of RP images. rpbeta is 1/kT in reduced units. rptype takes keywords of RPCYC (for ring polymer), RPLIN (for linear polymer) and RPFIX (for a linear polymer with fixed ends, provided in files xminA and xminB).*RINGPOLYMER*keyword takes the place of*POINTS*and must be the last keyword in the odata file before the points.*RKMIN gmax eps*: calculates a steepest-descent path using gradient only information with convergence criterion*gmax*for the RMS force and initial precision*eps*. A fifth order Runga-Kutta algorithm is used.*ROT*: if present a rotational kinetic energy term is added to the Hamiltonian. Either constant angular momentum (*ROT JZ x*) or constant angular velocity (*ROT OMEGA x*) may be used to specify*J*_{z}or*ω*_{z}.*RPPROJEXTRA*: for`RINGPOLYMER`project out the coordinate corresponding to cyclic permutation of beads in the`BFGSTS`Rayleigh-Ritz procedure. This mode can produce an additional zero eigenvalue if the number of beads is large enough.*SCALE n*: sets the scaling algorithm for eigenvector-following steps, as described in §8. The default is*n*=10.*SCORE_QUEUE*: specifies an Score parallel environment. Currently not used on group clusters.*SEARCH n*: specifies the search type for eigenvector-following and steepest-descent calculations based on second derivatives and Hessian diagonalisation, default is type 0. The most common options are 0, a minimisation, and 2, a transition state search. See §5 for full details.*SHIFT x*: specifies the shift applied to eigenvectors corresponding to normal modes that conserve the energy. The default is 10^{6}. The shift*must*be large enough to move the eigenvalues in question to the top of the spectrum.*SLERP*: activates the iSLERP algorithm for rigid bodies when interpolating an initial band for the NEB. This algorithm (due to Li, X., J. Graphics Tools**12**(3), 1 (2011)) uses quaternions to provide an efficient route to smooth interpolation of a rigid body between two endpoints. Without this keyword, default behaviour is to interpolate rigid body coordinates as though they were cartesian. This is often not a problem, but can lead to uneven interpolation and occasionally very bad interpolated bands. The iSLERP algorithm seems to give reliably good interpolations.*SPRING type limit factor*: specifies the use of a surrogate spring potential. For ReaxFF (or other potentials) we may need to restrain some bonds to a specified value to avoid reactions. In such cases, the surrogate spring potential should be added between one or more pairs of atoms in the system.*type*specifies the type of spring: either*harmonic*or*reaxff*.*limit*(*neb*or*none*) specifies whether we should limit its operation. Currently, the surrogate potential can be limited to operate only during a*neb*stage or without any limitation whatsoever, i.e.*none*.*factor*(default: 0.95) specifies a value that multiplies the spring constant(s) in each call to potential. The lowering of spring constant(s) can be used to recover the original potential at the end of the NEB stage. A file called`springfile`is required to specify the pairs of atoms to be restrained together with the associated spring constants and bond length restraints. The syntax of`springfile`is the following:

N

At_{i}At_{j}K_{ij}R_{ij}

Where N is the total number of listed bonds, At

_{i}and At_{j}are atom ID's, K_{ij}is a spring constant and R_{ij}is a bond restraint length. In case of a*reaxff*type spring, an additional spring constant should be listed immediately after the 1^{st}spring constant. Values for the spring constants are potential and system dependent. For a ReaxFF system, a typical value for the 1^{st}(2^{nd}) spring constant is 1*E*7 (2.5). When PERMDIST is active, a`springfile.perm`will be generated and used for the (optimally) aligned structure with the permuted atom indices.*SQVV NIterSQVVGuessMax SQVVGuessRMSTol*: specifies that the first*NIterSQVVGuessMax*DNEB refinements should be done using the SQVV algorithm, rather than LBFGS.[18] The DNEB optimisation will switch to LBFGS minimisation after*NIterSQVVGuessMax*steps or if the RMS force falls below*SQVVGuessRMSTol*. The default values for*NIterSQVVGuessMax*and*SQVVGuessRMSTol*are 300 and 2.0, respectively.*ST muD E*: calls a finite system of Stockmayer particles, where*μ*_{D}is the dipole moment strength and the electric field of stength*E*can be optionally present. The field, if present, is along the space-fixed z-direction.*STEPMIN n*: sets the minimum number of optimisation steps before convergence will be tested. The default is zero.*STEPS n*: sets the maximum number of optimisation steps per call to`OPTIM`. The default is*n*=1. Setting*n*to zero at the start of a run means that only a point group analysis is performed.*STOCK*: sets the dipole moment strength and attraction prefactor in the Stockmayer potential,*μ**λ**V*_{ij}= 4*r*_{ij}^{-12}-*λr*_{ij}^{-6}+ ⋅ - (⋅)(⋅).*STOCKSPIN*.*STOCKSPIN x n*: Activates checking for alignment of dipoles with the*z*axis in the Stockmayer potential. Such alignment makes the polar angle*φ*for the dipole redundant, leading to extra zero Hessian eigenvalues and associated problems. If alignment is detected at any step in an optimisation then the orientation of the cluster is randomised and a warning is printed.*x*is the amount by which | cos*θ*| may differ from 1 for the dipole to be counted as aligned with the*z*axis.*n*is the maximum number of attempts to remove aligned dipoles by random rotation. Values of 10^{-4}and 10, respectively, are a sensible starting point.*STOPDIST x*: in a*CONNECT*run, stop as soon as the distance between the initial (*x*> 0) or final (*x*< 0) minimum and the furthest connected minimum exceeds |*x*|.*STOPFIRST*: in a*CONNECT*run, stop as soon as the initial minimum has a transition state connection.*SUMMARY n*: prints a summary of the steps and derivatives every*n*steps. The default is*n*= 20.*SYMCUT x*: specifies the RMS force below which the point group symmetry subroutine will be called. The default is*x*=0.001.*TAG num massfac*: allows atoms to be tagged. Atom number*num*has its mass increased by a factor*massfac*for point group symmetry assignment only. To tag more than one atom use additional*TAG*lines in`odata`.*TD*: add a tetrahedral field of strength*x*to the potential.*TIMELIMIT x*:`OPTIM`will stop if the accumulated cpu time exceeds*x*seconds. The default value is infinity.*TOLD x*: sets the initial distance tolerance for points to be considered the same after rotations and reflections in point group determination. The default is 0.0001.*TOLE x*: sets the initial tolerance for eigenvalues of the inertia tensor to be considered equivalent in point group determination. The default is 0.0001.*TOMEGA*: includes omega angles in the*TWISTDIHE*list.*TOSI*: specifies a Born-Mayer potential with the parameters indicated (see §4).*A*_{++}*A*_{–}*A*_{+-}*ρ**TOSIC6 c6pp c6mm c6pm*: specifies additional C6 dispersion coefficients for the*TOSI*potential.*c6pp, c6mm*, and*c6pm*should be the values of the C6 parameters between positive ions, negative ions and positive and negative ions in atomic units (see §4).*TOSIPOL alphap alpham damp*: specifies cation and anion polarisabilities in atomic units and a damping parameter for the*TOSI*potential (see §4).*TRAD x*: sets the trust radius (see §8). The default value is 2.0.*TRAP k n*: general trapped ion potential coded by Ersin Yurtsever. The form of the potential is*V*=*r*_{i}^{n}+ ,*r*_{i}is the distance of ion*i*from the origin and*r*_{ij}is the distance between ions*i*and*j*.*TSIDECHAIN*: includes sidechain angles in the*TWISTDIHE*list.*TSPLITTING*: Tunnelling splittings of the vibrational ground state level following [35]. Every time a rate is calculated, the tunnelling splitting is calculated as well. Tunnelling splittings only make sense for symmetric molecules and barriers.*TTM3*: specifies Xantheas' TTM3-F water potential, coded by Jeremy Richardson. The atom order must be O1, O2,..., H1a, H1b, H2a, H2b,.... The energy is in kcal/mol and the distance unit is Å. Hydrogens are NOT permutable between different oxygens.*TWIST n1 n2 n3 n4 f ref*: adds a twist potential corresponding to the torsional angle for atoms*n1*,*n2*,*n3*and*n4*. The functional form is*V*_{twist}(*φ*) =*f*sin(*φ*-*φ*_{ref}.*phi*_{ref}and the angular displacement are set to the range -*π*to*π*, but with the sin function dependence this should now make no difference. Setting*φ*_{ref}to the angle for the global minimum or native state might be convenient.*TWISTDIHE random xpert*: twist phi/psi dihedral angle selected from an array of safely twistable dihedrals using the random number*random*between 0 and 1 by*xpert*degrees before starting optimisation. This keyword is no longer designed to be user specified, but is used by PATHSAMPLE.*TWISTTYPE n*: integer*n*specifies the type of dihedral angle twisting used to guess transition states in**guessts**for CHARMM and UNRES. The recommended value is*n*=5. See also*NORANDOM*.*TWOENDS fstart finc ntwo rmstwo ntwoiter twoeval*: obsolete: specifies a double-ended transition state search.*fstart*is the initial force constant pulling the coordinates towards the final geometry which is read from a file named`final`.*finc*is the increment for the force constant after each cycle.*ntwo*is the maximum number of minimisation steps taken after each increment of the force constant, and*rmstwo*is the convergence condition on the RMS force for these minimisations.*ntwoiter*is the total number of force constant increments allowed and*twoeval*is the value of the smallest Hessian eigenvalue below which the program will shift to a transition state search.*UACHIRAL*: MUST be included when using ff03ua, the AMBER united atom forcefield. It ensures the correct impropers are used to define sidechain chirality when HB hydrogen is missing.*UNRES*: specifies the UNRES potential, which requires an UNOPTIM executable. An auxiliary file`coords`is required.*UNRES*must be the last OPTIM directive in the`odata`file. The remaining content of`odata`consists of UNRES keywords and setup information.*UPDATES mupdate1 mupdate2 mupdate3 mupdate4*: specifies the number of updates in the LBFGS routine before resetting.*mupdate1*is used for energy minimisation,*mupdate2*is currently ignored by**mind**,*mupdate3*is used in Rayleigh-Ritz eigenvalue calculations, and*mupdate4*is used in NEB and DNEB optimisation.*mupdate5*is used in string method optimisation. The default value is 4 for all five parameters.*USEDIAG n*: allows different approximations to be used for the eigenvalue in a Rayleigh-Ritz*BFGSTS*calculation.*n*= 1 specifies the second order central differences method.*n*= 2 is the same accuracy, but uses a formula that minimises the rounding error, which may work better for numerically large values of the energy and is the default behaviour.*n*= 3 specifies the first order forward finite differences method which is less accurate, but requires one fewer potential call per iteration.*USEEV n*: specifies the number of non-zero (lowest) eigenvalues and eigenvectors to be calculated by LAPACK routine DSYEVR in**efol.f**,**bfgsts.f**or**hybridmin.f**. If this value is not specified than full diagonalisation is performed in**efol.f**using LAPACK routine DSYEV, while the default is a single eigenvalue/eigenvector for**bfgsts.f**and**hybridmin.f**.*VALUES n*: prints the Hessian eigenvalues every*n*steps. The default is*n*=20.*VARIABLES*: optimises a general function (which must be specified in**potential**. The initial values of the variables are read one per line after the*POINTS*keyword in`odata`.*VARSTEPOPT*: Allows instanton optimization with a variable step size distributino of the beads as described in [36].*VASP vaspjob*: tells`OPTIM`to use the`VASP`executable to calculate energies and gradients. The string*vaspjob*specifies the run command for`VASP`, for example on CSD3:

VASP 'mpirun -ppn 16 -np 16 /home/bk393/APPS/vasp.5.4.4/with-VTST/bin/vasp_std > vasp.out'

The setup has been changed so that both start and finish coordinates are read from files in the VASP POSCAR format. The coordinates can be Cartesian or fractional (Direct keyword in POSCAR). PPOSCAR files can be visualised directly with ase (Atomic Simulation Environment). To access this program on volkhan:

module load anaconda/python3/5.3.0

pip install ase –user

ase-gui POSCAR1.vasp &

which assumes that /.input/bin is in the current $PATH environment variable.*VECTORS n*: prints the Hessian eigenvectors every*n*steps. Eigenvector printing is turned off by default.*WARRANTY*: print warranty information.*WELCH*: specifies a Welch binary salt potential with the parameters indicated (see §4).*A*_{++}*A*_{–}*A*_{+-}*ρ**Q*_{+}*Q*_{-}*α*_{+}*α*_{-}*XTB system runparams*: provides an interface to the xtb program; see the documentation at xtb-docs.readthedocs.io/en/latest/contents.html.*system*is a string with a name for the job;*runparams*is a string with options for the xtb executable, which must be in the current path. For example:

XTB water21 '–acc 0.1 –gfn2 -P 8' Note:`OPTIM`assumes that the coordinates are in Å, which needs a $coords angs directive in the xtb input file. There is a conversion factor in the gradient, to account for xtb gradient printing in hartree/bohr even when the coordinates are in Å.*ZEROS n*: sets the number of zero Hessian eigenvalues to be assumed—useful for general optimisation problems specified by*VARIABLES*.