CREST command line arguments

Contents

• CREST command line arguments

  • General and techincal options

    • Runtypes

    • Ensemble sorting

  • Options

    • Calculation settings passed to xtb

    • Options related to molecular dynamics and metadynamics simulations

    • Options for conformational search algorithms

    • Options related to constrainment

  • Other tools

CREST is usually invoked via commandline, and requires only a coordinate input file. The program supports the TURBOMOLE coordinates (coord, Bohr), Xmol (*.xyz, Angstroem) or 3d SDF (V2000,V3000) formats and can be called via

> crest [INPUT] [OPTIONS]

If no file is given as [INPUT], then CREST automatically searches for a file called coord in the TURBOMOLE format. Either must be present. The different [OPTIONS] are listed below and refer to Version 2.11 of the CREST code. [DEFAULT] options do not need to be specified explicitly.

General and techincal options

Flag	Description
-h,-help	Print an overview of most available options (i.e., this site)
--version	Print only the program header and disclaimer.
--cite	Print the most relevant citations.
--xnam BIN	Specify the name (and path) of the xtb binary that should be used as BIN. The [DEFAULT] is xtb.
--niceprint	In-line progress bar printout for optimizations.
--scratch <DIR>	Performs the entire calculation in the specified <DIR>. If <DIR> is not existing it will be created.
--T <INT>	Specify the number of CPU threads <INT> that shall be used. CREST automatically adjusts the number of processes according to this variable in each step, in order to achieve optimal parallelization of the calculations.
--dry	Perfrom a “dry” run, i.e., nothing is actually done but instead an overview of the settings that would be applied in the calculation is given.

Runtypes

Several different applications are availabile within the CREST program. The most important usage are the two different conformational search algorithms MF-MD-GC and iMTD-GC, but there are also some smaller utility tools that can be used, such as an CRE sorting function (CREGEN), or a standalone z-martix sorting function (ZSORT). The different runtypes are:

Algorithm	Flag	Description
MF-MD-GC algorithm (outdated)	--v1	First generation of the GFNn-xTB driven conformational search algorithm, consisting out of mode following, molecular dynamics sampling and genetic structure crossing.
MTD-GC algorithm (outdated)	--v2	Second generation of the GFNn-xTB driven conformational search algorithm, consisting out of a meta-dynamics approach and genetic structure crossing.
iMTD-GC algorithm [DEFAULT]	--v2i, --v3	Iterative version of the MTD-GC workflow, which is the default runtype of CREST.
iMTD-sMTD algorithm	--v4	Iterative workflow, making use of static metadynmics simulations.
Conformational entropy algorithm	--entropy	Specialized version of the iMTD-sMTD workflow, specialized in the calculation of conformational entropy.

Ensemble sorting

CREGEN ensemble sorting tool for standalone use

Flag	Description
--cregen <FILE>	Tool to sort a given ensemble <FILE> according to energy, atomic RMSD and rotational constant. A reference structure (e.g. coord) has to be provided.
--ewin <REAL>	Set the energy threshold to REAL kcal/mol. This affects several runtypes and the [DEFAULT] is depending on the application (6 kcal/mol conformational searches, 30 kcal/mol screening tools).
--prsc	Create a scoord.`*` file for each conformer in the TURBOMOLE format.
--rthr <REAL>	Set RMSD threshold in Ångström. The [DEFAULT] is 0.125 Å.
--ethr <REAL>	Set energy threshold between conformer pairs in kcal/mol. The [DEFAULT] is 0.05 kcal/mol.
--bthr <REAL>	Set lower bound for the rotational constant threshold to REAL. The [DEFAULT] is 0.01 (= 1%). The thresold is dynamically adjusted between this value and 2.5%, based on the anisotropy of the rotational constants.
--nmr, --eqv, --entropy	Activate determination and printout of NMR-equivalencies. Writes the files anmr_rotamer and anmr_nucinfo, which are required by the ENSO python script.
--athr <REAL>	Similarity threshold to determine internal rotation of equal atoms for NMR. The [DEFAULT] is 0.04.
-temp <REAL>	Set temperature for the calculation of Boltzmann weights. The [DEFAULT] is 298.15 K.
--esort	Sort only based on energy (i.e., no RMSD and rotational constant comparison)
--nowr	Don’t write new ensemble files (crest_rotamers_`*`.xyz, crest_conformers.xyz)
--subrmsd	Compare only those parts of the structure that were also included in the metadynamics bias potential. Can be important for constrained conformational searches.
--notopo	Turn off the initial topology check of the structures in the ensemble.

An extension to the CREGEN sorting is an automatic principle component analysis (PCA) and k-Means sorting clustering algorithm. It can be invoked with the --cluster command.

Flag	Description
--cluster <INT>	Perform a clustering on the final CREGEN ensemble to identify INT most representative structures, based on dihedral angles. Note that this algorithm currently does not work well for non-covalent complexes or molecular clusters and should only be applied to singular molecules.

Options

Calculation settings passed to xtb

Method selection

Flag	Description
--gfn2, --gfn1, --gfn0, --gfnff	Use any of the respective GFNn methods. The default is GFN2-xTB but GFN-FF is strongly recommended for faster sampling.

Charge and multiplicity

Flag	Description
--chrg <INT>	Specify molecular charge as INT, overrides .CHRG file.
--uhf <INT>	Specify \(N_{\alpha}-N_{\beta}\) as INT, overrides .UHF file

Implicit solvation

Flag	Description
--g, --gbsa <SOLVENT>	Generalized born (GB) model with solvent accessable surface (SASA) model, for available SOLVENT options see Implicit Solvation. The solvent input is not case-sensitive.
--alpb <SOLVENT>	New ALPB implicit solvation model, for available SOLVENT options see Implicit Solvation. The solvent input is not case-sensitive.

Geometry optimization thresholds

Flag	Description
--opt <LEVEL>	Set the optimization accuracy for final GFNn–xTB optimizations. See Geometry Optimization for valid LEVEL arguments. The [DEFAULT] is vtight.

Options related to molecular dynamics and metadynamics simulations

Flag	Description
--mdlen, --len <REAL>	The length of the metadynamics simulations (MTD) in CREST is usually determined automatically, but with this flag it can be set to REAL (in ps). It is also possible to set a multiple of the automatically determined length by using x<REAL> instead, where REAL then is a multiplicative factor (e.g. x0.5 for half the default simulation length).
--shake <INT>	Set SHAKE mode for MD. INT can be 0(= off), 1(= H-only), or 2(= all bonds). The [DEFAULT] is 2.
--tstep <INT>	Set MD time step to INT fs. The [DEFAULT] is 5 fs for GFNn-xTB calculations (requires SHAKE), and 1.5 fs for GFN-FF. The timestep is also automatically checked with a trial simulation at the beginning of the conformational search.
--mddump <INT>	Set dumpstep in which coordinates are written to the trajectory file to INT fs. The [DEFAULT] is 100 fs.
--vbdump <REAL>	Set dump frequency in which a new reference structure is taken for \(V_{bias}\) to REAL ps. The [DEFAULT] is 1.0 ps.

Options for conformational search algorithms

Z-matrix sorting (see also --zsort above)

Flag	Description
--zs	Perform z-matrix sorting (i.e. ZSORT) for the input coordinate file.
--nozs	[DEFAULT] Do not perform z-matrix sorting of the input file.

Genetic Z-matrix crossing

Flag	Description
--cross	[DEFAULT] Perform Z-matrix strucutre crossing (GC) in the algorithm.
--nocross	Skip Z-matrix strucutre crossing.

Additional MD sampling after MTD

Flag	Description
--norotmd	Turn off the additional MDs on the lowest conformers after the MTD step.
--tnmd <REAL>	Set temperature for the additional normal MDs on the lowest conformers after the MTD step. The [DEFAULT] is 400 K.

Adjusting iterative behavior of iMTD-GC

Flag	Description
--mrest <INT>	Maximum number of MTD restarts in iMTD-GC algorithm. The [DEFAULT] is 5 cycles.

Special settings for the iMTD-GC workflow

Flag	Description
--quick	Perform a search with reduced settings for a crude conformer ensemble.
--squick, --superquick	Perform an even more crude conformational search than with -quick.
--mquick	Perform an even more crude conformational search than with -quick or -squick.
--nci	Specialized NCI mode that can be used to find aggregates of NCI complexes. The option generates an ellipsoide potential around the input structure and adds it to the MTD simulation. Also, settings for \(k\) and \(\alpha\) are adjusted and some settings are reduced, in order to achieve lower computation times.
---wscal <REAL>	Scale the ellipsoide potential axes in the --nci mode by factor REAL.

Technical iMTD-GC settings

Flag	Description
--keepdir	Keep sub-directories of the conformer production run.

Property mode appendix

Flag	Description
--prop <STR>	This initializes the usage of the “property” mode as an appendix to the regular conformational search. STR defines what shall be done with the ensemble.
--for,--forall <FILE>	Instead of starting the property calculation on the final conformer ensemble file after iMTD-GC the property mode can directly be started for a given input ensemble <FILE> in the Xmol (*.xyz) format.

Valid options for STR are currently (case sensitive!):

Option	Description
hess	performs a hessian calculation for all conformers and re-weights the ensemble on free energies
reopt	reoptimization of the ensemble with vtight thresholds (usefull for “quick” runs)
autoIR	calculate vib. modes for all conformers and average them (weighted by Boltzmann populations) in a single “crest.vibspectum” file.

Note

The different quick, NCI and property settings are incompatible with --entropy!

Entropy mode settings

Flag	Description
--scthr,--entropy_cthr <REAL>	Specifiy the ensemble growth threshold (% new conformers) for --entropy and --v4 convergence. The default is 0.02 (=2%) for the entropy mode and 0.05 (=5%) for --v4.
--ssthr,--entropy_sthr <REAL>	Specifiy the entropy growth threshold (% growth entropy) for --entropy and --v4 convergence. The default is 0.005 (=0.5%) for the entropy mode and 0.01 (=1%) for --v4.
--trange <from> <to> <step>	Entropies from the --entropy mode are always printed for a range of temperatures. The respective temperatures can be specified with this option.
--ptot <REAL>	For the rovibrational average \(\overline{S}_{msRRHO}\) requires frequency calculations at GFN level. To reduce computational cost, only the specified REAL fraction of structures are calculated, and the rest is averaged. The default is 0.9 (=90%).
--fscal <REAL>	Scale frequencies read for \(\overline{S}_{msRRHO}\) by a given factor. Also works together with the --thermo option (see below, section Other Tools)
--rotorcut,--sthr	Specify the rotor cutoff for the ro/vib entropy interpolation (\(\tau\)). Also works together with the --thermo option (see below, section Other Tools)

Options related to constrainment

Flag	Description
--cinp <FILE>	Specify a <FILE> with additional constraints in the xTB syntax.
--constrain <atom list>	Set up an example file in which the atoms in <atom list> shall be constrained. The file will be called .xcontrol.sample. No calculations will be performed and the run is aborted after this sample is wirtten. The written file can be read with the --cinp option.
--cbonds [REAL]	Set up a constraint on all bonds (as detected in the input coordinates topology), where [REAL] optionally can be used to set the force constant (default value 0.02 Eh)
--cmetal [REAL]	Set up a constraint on all M-X bonds (as detected in the input coordinates, M = transition metal atom), where [REAL] optionally can be used to set the force constant (default value 0.02 Eh)
--cheavy [REAL]	Set up a constraint on all heavy atom bonds (i.e., X-H bonds will be not constrained), where [REAL] optionally can be used to set the force constant (default value 0.02 Eh)
--clight [REAL]	Set up a constraint on all X-H bonds (as detected in the input coordinates), where [REAL] optionally can be used to set the force constant (default value 0.02 Eh)
--fc <REAL	Specifiy a force constant for the applied constaints (default value 0.02 Eh). Note: Only one force constant is applied for all constraints!

Other tools

ZSORT z-matrix sorting tool

Flag	Description
--zsort	The atom order of the given input file is sorted in order to yield a more consistent z-matrix, i.e., atoms are grouped together according to the molecular structure (e.g. methyl groups).

MDOPT parallel ensemble optimization

Flag	Description
--mdopt <FILE>	Optimize each point on a given trajectory or ensemble file <FILE> with GFNn–xTB.

SCREEN ensemble screening tool

Flag	Description
--screen <FILE>	Optimize each point on a given trajectory or ensemble file <FILE> with GFNn–xTB in a multilevel approach and sort the resulting ensemble (CREGEN).

Automated protonation site screening

Flag	Description
--protonate	A tool that can be used to find protonation sites, i.e., the protomers of the input structure. In the approach first localized molecular orbitals (LMOs) are calculated and LP- and π-centers are identified. Then, a proton is added to each of these centers and the resulting structures are optimized and sorted.

Modifier	Description
--swel <STR>	Change H\(^+\) in the protonation tool to some other ion specified by STR. STR has to contain the element symbol AND charge, e.g. Na+ or Ca2+

Automated deprotonation site screening

Flag	Description
--deprotonate	A tool to find deprotomers of the input structure. Each H atom is removed and the resulting structures are optimized and sorted.

Automated tautomerization screening

Flag	Description
--tautomerize	A tool that combines the -protonate and -deprotonate options to find (prototropic) tautomers of the input structure.

Modifier	Description
--trev	Reverse order of operation for tautomerization mode, i.e., first deprotonate and then protonate.
--iter <INT>	Number of Protonation/Deprotonation Iterations for -tautomerize mode. The [DEFAULT] is 2 iterations.

Ensemble comparison

Flag	Description
--compare <FILE1> <FILE2>	Compare two ensembles <FILE1> and <FILE2>. Both ensembles must have the same order of atoms of the molecule and should contain rotamers (e.g. crest_rotamers.xyz). Furthermore the structures should have energies in the same magnitude, or relative energies as the comment in the ensemble file.

Modifier	Description
--maxcomp <INT>	Selcect the lowest INT conformers out of each ensemble to be compared with -compare. The [DEFAULT] is the 10 lowest conformers.

Rovibrational entropy average

Flag	Description
--rrhoav <FILE>	Calculate the \(\overline{S}_{msRRHO}\) term for a specified ensemble. The --rrhoav option can be modified with the same settings as the entropy mode (e.g. --trange).

Modifier	Description
--printpop	Write files with free energy Boltzmann populations for each --trange temperature into a separate directory called populations.

RMSD comparison

Flag	Description
--rmsd,--rmsdheavy <FILE1> <FILE2>	Calculate the RMSD or heavy atom RMSD between two given structures. Input format of the two structures can be any of the formats that can be read by CREST, output will always be the RMSD in Angstroem.

Topology check

Flag	Description
--testtopo <FILE>	Calculate the topology (neighbour lists) for a given input structure and print to info to screen.

Thermostatistical calculations from frequencies

Flag	Description
--thermo <FILE>	Calculate thermo data for given structure. Also requires vibrational frequencies in the Turbomole format, saved as file called vibspectrum.

Modifier	Description
--fscal, --rotorcut,--sthr	(see above)

Splitting an Ensemble into seperate files

Flag	Description
--splitfile <FILE> [from] [to]	Split an ensemble from <FILE> into seperate directories for each structure. [from] and [to] can be used to select specific structures from the file or a range of structures. The new directories are collected in the SPLIT directory.