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NAME

OpenFECalculateAbsoluteBindingFreeEnergy.py - Calculate absolute binding free energy

SYNOPSIS

OpenFECalculateAbsoluteBindingFreeEnergy.py [--abfeParams <Name,Value,...>] [--executeDAGParams <Name,Value,..>] [--loggingLevel <Info, Warning or Error>] [--mode <FirstMolecule, AllMolecules, or ...>] [--missingChargeMode <Calculate or Stop>] [--moleculeNames <MolName1,MolName2,..>] [--outfilePrefix <text>] [--overwrite] [--resultFileParams <Name,Value,..>] [--solventParams <Name,Value,...>] [--smallMolFileParams <Name,Value,...> ] [-w <dir>] -i <infile> -s <smallmolfile> -o <outifiledir>

OpenFECalculateAbsoluteBindingFreeEnergy.py -l | --list

OpenFECalculateAbsoluteBindingFreeEnergy.py -h | --help | -e | --examples

DESCRIPTION

Calculate Absolute Binding Free Energy (ABFE) for molecules in a small molecule input file. You may calculate ABFEs for specific molecules or all molecules in the input file.

The input file must contain a macromolecule already prepared for simulation. The preparation of the macromolecule for a simulation generally involves the following tasks: identification and replacement of non-standard residues; addition of missing residues; addition of missing heavy atoms; addition of missing hydrogens.

In addition, the small molecule input file must contain molecules already prepared for simulation. It must contain appropriate 3D coordinates relative to the macromolecule along with no missing hydrogens.

The MD simulation workflow, employed for the calculation of ABFEs, involves the following steps:

Each complex and solvent simulation, by default, may run for 16.75 and 11.8 nanosecond respectively, for a total of 28.55 nanoseconds. The total MD simulation time for correspond to 85.66 nanosecond to repeat the protocol 3 times for the complex and solvent simulations.

Possible outfile prefix:

Possible output directories:

Possible output files and directories under <OutfileDir>:

OPTIONS

-a, --abfeParams <Name,Value,...> [default: auto]

A comma delimited list of parameter name and value pairs for ABFE protocol settings employed during the calculation of ABFEs.

The default values are automatically updated to match settings provided by OpenFE module AbsoluteBindingProtocol.

You must specify valid OpenFE values for these parameters. An extensive validation is not performed.

The supported parameter names along with their default values are are shown below: explain and doc...

protocolRepeats, 3

Complex equil output settings:

complexEquilOutputCheckpointInterval, 1 [ Units: picosecond ]
complexEquilOutputCheckpointStorageFilename, checkpoint.chk
complexEquilOutputEquilNPTStructure, equil_npt_structure.pdb
complexEquilOutputEquilNVTstructure, equil_nvt_structure.pdb
complexEquilOutputForcefieldCache, db.json
complexEquilOutputLogOutput, production_equil_simulation.log
complexEquilOutputMinimizedStructure, minimized.pdb
complexEquilOutputIndices, all [ Possible value: Any valid
     selection. ]
complexEquilOutputPremnimizedStructure, system.pdb
complexEquilOutputProductionTrajectoryFilename, production_equil.xtc
complexEquilOutputTrajectoryWriteInterval, 20.0 [ Units:
     picosecond ]

Complex equil simulation settings:

complexEquilSimulationEquilibrationLength, 0.5 [ Units: nanosecond ]
complexEquilSimulationEquilibrationLengthNVT, 0.25 [ Units:
     nanosecond ]
complexEquilSimulationMinimizationSteps, 5000
complexEquilSimulationProductionLength, 5.0 [ Units: nanosecond ]

Complex lambda settings:

complexLambdaElec, 0.0 0.0 0.0 0.0 0.0 0.0 0.1 0.2 0.3 0.4 0.5 0.6
     0.7 0.8 0.9 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0
     1.0 1.0 [ Possible values: A space delimited list of values
     between 0.0 and 1.0 ]
complexLambdaRestraints, 0.0 0.2 0.4 0.6 0.8 1.0 1.0 1.0 1.0 1.0
     1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0
     1.0 1.0 1.0 1.0 [ Possible values: A space delimited list of
     values between 0.0 and 1.0 ]
complexLambdaVdw, 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
     0.0 0.0 0.0 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.65 0.7 0.75 0.8 0.85
     0.9 0.95 1.0 [ Possible values: A space delimited list of values
     between 0.0 and 1.0 ]

Complex output settings:

complexOutputCheckpointInterval, 1.0 [ Units: nanosecond ]
complexOutputCheckpointStorageFilename, complex_checkpoint.nc
complexOutputForcefieldCache, db.json
complexOutputFilename, complex.nc
complexOutputIndices, not water [ Possible value: Any valid
     selection. ]
complexOutputStructure, alchemical_system.pdb
complexOutputPositionsWriteFrequency, 100 [ Units: nanosecond ]
complexOutputVelocitiesWriteFrequency, None [ Possible
     values: > 0; Units: picosecond ]

Complex simulation settings:

complexSimulationEarlyTerminationTargetError, 0.0 [ Units:
     kilocalorie_per_mole ]
complexSimulationEquilibrationLength, 1.0 [ Units: nanosecond ]
complexSimulationMinimizationSteps, 5000
complexSimulationNReplicas, 30
complexSimulationProductionLength, 10.0 [ Units: nanosecond ]
complexSimulationRealTimeAnalysisInterval, 250.0 [ Units:
     picosecond ]
complexSimulationRealTimeAnalysisMinimumTime, 500.0 [ Units:
     picosecond ]
complexSimulationSamplerMethod, repex [ Possible values: repex,
     sams, or independent ]
complexSimulationSamsFlatnessCriteria, logZ-flatness [ Possible
     values: logZ-flatness, minimum-visits or histogram-flatness ]
complexSimulationSamsGamma0, 1.0
complexSimulationTimePerIteration, 2.5 [ Units: picosecond ]

Complex solvation settings:

complexSolvationBoxShape, dodecahedron [ Possible values: cube,
     dodecahedron, or octahedron ]
complexSolvationBoxSize, None [ Possible value: A triplet of space
     X Y Z values; Units: nanometer ]
complexSolvationSolventModel, tip3p [ Possible values: tip3p, spce,
     tip4pew, or tip5p ]
complexSolvationSolventPadding, 1.0 [ Units: nanometer ]

Engine settings:

engineComputePlatform, CPU [ Possible values: CPU, CUDA,
     OpenCL, or Reference ]
engineGpuDeviceIndex, None [ Possible values: 0, 0 1, etc. ]
Forcefield settings:

forcefieldConstraints, HBonds [ Possible values: HBonds,
     AllBonds, or HAngles ]
forcefields, amber/ff14SB.xml amber/tip3p_standard.xml
     amber/tip3p_HFE_multivalent.xml amber/phosaa10.xml
     [ Possible values: A space delimited list of valid names. ]
forcefieldHydrogenMass, 3.0 [ Units: amu ]
forcefieldNonbondedCutoff, 0.9 [ Units: nanometer ]
forcefieldNonbondedMethod, PME [ Possible values: PME or
     NoCutoff ]
forcefieldRigidWater, yes, [ Possible values: yes or no ]
forcefieldSmallMoleculeForcefield, openff-2.1.1 [ Possible
     value: A valid forcefield name. ]

Integrator settings:

integratorBarostatFrequency, 25.0 * timestep [ The specified value
     is a multiple of integratorTimestep. ]
integratorConstraintTolerance, 1e-06
integratorLangevinCollisionRate, 1.0 [ Units: 1 / picosecond ]
integratorNRestartAttempts, 20
integratorReassignVelocities, no [ Possible values: yes or no ]
integratorRemoveCom, no [ Possible values: yes or no ]
integratorTimestep, 4.0 [ Units: femtosecond ]

Partial charge settings:

partialChargeNaglModel, None [ Default: Production AM1BCC model for
     NAGL; Possible value: Any valid name. ]
partialChargeNumberOfConformers, None [ Possible value: > 0 ]
partialChargeOffToolkitBackend, AmberTools [ Possible values:
     AmberTools or RDKit ]
partialChargeMethod, AM1BCC [ Possble values: AM1BCC, Espaloma,
     or NAGL ]

Restraint settings:

restraintKPhiA, 334.72 [ Units: kilojoule_per_mole / radian**2
     The default value is equivalent to 80 kcal/mo/radian**2 ]
restraintKPhiB, 334.72 [ Units: kilojoule_per_mole / radian**2 ]
     The default value is equivalent to 80 kcal/mo/radian**2 ]
restraintKPhiC, 334.72 [ Units: kilojoule_per_mole / radian**2 ]
     The default value is equivalent to 80 kcal/mo/radian**2 ]
restraintKR, 4184.0 [ Units: kilojoule_per_mole / nanometer**2 The default value is equivalent to 10 kcal/mol/angstrom**2
restraintKThetaA, 334.72 [ Units: kilojoule_per_mole / radian**2 ]
     The default value is equivalent to 80 kcal/mo/radian**2 ]
restraintKThetaB, 334.72 [ Units: kilojoule_per_mole / radian**2
     The default value is equivalent to 80 kcal/mo/radian**2 ]
restraintAnchorFindingStrategy, bonded [ Possible values:
     multi-residue or bonded ]
restraintDsspFilter, yes [ Possible values: yes or no ]
restraintHostMaxDistance, 1.5 [ Units: nanometer ]
restraintHostMinDistance, 0.5 [ Units: nanometer ]
restraintHostSelection, backbone [ Possible value: Any valid
     selection. ]
restraintRmsfCutoff, 0.1 [ Units: nanometer ]

Solvent equil output settings:

solventEquilOutputCheckpointInterval, 1.0 [ Units: nanosecond ]
solventEquilOutputCheckpointStorageFilename, checkpoint.chk
solventEquilEquilOutputNPTStructure, equil_npt_structure.pdb
solventEquilEquilNVTOutputStructure, equil_nvt_structure.pdb
solventEquilOutputForcefieldCache, db.json
solventEquilOutputLogOutput, production_equil_simulation.log
solventEquilOutputMinimizedStructure, minimized.pdb
solventEquilOutputIndices, all [ Possible value: Any valid
     selection. ]
solventEquilOutputPreminimizedStructure, system.pdb
solventEquilOutputProductionTrajectoryTilename, production_equil.xtc
solventEquilOutputTrajectoryWriteInterval, 20.0 [ Units:
     picosecond ]

Solvent_equil_simulation_settings:

solventEquilSimulationEquilibrationLength, 0.2 [ Units: nanosecond ]
solventEquilSimulationEquilibrationLengthNVT, 0.1 [ Units:
     nanosecond ]
solventEquilSimulationMinimizationSteps, 5000
solventEquilSimulationProductionLength, 0.5 [ Units: nanosecond ]

Solvent lambda settings:

solventLambdaElec, 0.0 0.25 0.5 0.75 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0
     1.0 1.0 [ Possible values: A space delimited list of values
     between 0.0 and 1.0 ]
solventLambdaRestraints, 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
     0.0 0.0 0.0 [ Possible values: A space delimited list of values
     between 0.0 and 1.0 ]
solventLambdaVdw, 0.0 0.0 0.0 0.0 0.0 0.12 0.24 0.36 0.48 0.6 0.7
     0.77 0.85 1.0 [ Possible values: A space delimited list of values
     between 0.0 and 1.0 ]

Solvent output settings:

solventOutputCheckpointInterval, 1.0 [ Units: nanosecond ]
solventOutputCheckpointStorageFilename, solvent_checkpoint.nc
solventOutputForcefieldCache, db.json
solventOutputFilename, solvent.nc
solventOutputIndices, not water [ Possible value: Any valid
     selection. ]
solventOutputStructure, alchemical_system.pdb
solventOutputPositionsWriteFrequency, 100.0 [ Units: picosecond ]
solventOutputVelocitiesWriteFrequency, None [ Possible
     values: > 0; Units: picosecond ]

Solvent simulation settings:

solventSimulationEarlyTerminationTargetError, 0.0 [ Units:
     kilocalorie_per_mole ]
solventSimulationEquilibrationLength, 1.0 [ Units: nanosecond ]
solventSimulationMinimizationSteps, 5000
solventSimulationNReplicas, 14
solventSimulationProductionLength, 10.0 [ Units: nanosecond ]
solventSimulationRealTimeAnalysisInterval, 250.0 [ Unit: picosecond ]
solventSimulationRealTimeAnalysisMinimumTime, 500.0 [ Units:
     picosecond ]
solventSimulationSamplerMethod, repex [ Possible values: repex,
     sams, or independent ]
solventSimulationSamsFlatnessCriteria, logZ-flatness [ Possible
     values: logZ-flatness, minimum-visits or histogram-flatness ]
solventSimulationSamsGamma0, 1.0
solventSimulationTimePerIteration, 2.5 [ Units: picosecond ]

Solvent solvation settings:

solventSolvationBoxShape, dodecahedron [ Possible values: cube,
     dodecahedron, or octahedron ]
solventSolvationBoxSize, None [ Possible value: A triplet of space
     X Y Z values; Units: nanometer ]
solventSolvationSolventModel, tip3p [ Possible values: tip3p, spce,
     tip4pew, or tip5p ]
solventSolvationSolventPadding, 1.5 [ Units: nanometer ]

Thermo settings:

thermoPh, None [ Possible values: > 0 ]
thermoPressure, 1.0 [ Units: bar ]
thermoRedoxPotential, None [ Possible values: A valid float.
     Units: millivolts (mV) ]
thermoTemperature, 298.15 [ Units: kelvin ]

A brief description of parameters, taken from OpenFE documentation, is provided below:

protocolRepeats: Number of completely independent repeats of the
     entire sampling process.

Complex settings:

Complex parameters for the system, including the solvent model and
the solvent padding.

Complex equil output settings:

Parameters controlling simulation output during equilibration
phase of complex transformation.

complexEquilOutputCheckpointInterval: Frequency to write the
     checkpoint file.
complexEquilOutputCheckpointStorageFilename: Checkpoint filename.
complexEquilOutputEquilNPTStructure: NPT structure filename.
complexEquilOutputEquilNVTstructure: NVT strucure filename.
complexEquilOutputForcefieldCache: Filename for caching small
     molecule residue templates.
complexEquilOutputLogOutput: Simulation log filename.
complexEquilOutputMinimizedStructure: Minimized structire filename.
complexEquilOutputIndices: Selection string for selecting
     coordinates to write.
complexEquilOutputPremnimizedStructure: Initial structure filename.
complexEquilOutputProductionTrajectoryFilename: Trajectory filename.
complexEquilOutputTrajectoryWriteInterval: Frequency for writing
     velocities to trajectory file.

Complex equil simulation settings:

Parameters controlling simulation during equilibration phase of
complex transformation.

complexEquilSimulationEquilibrationLength: Length of the NPT
     equilibration phase.
complexEquilSimulationEquilibrationLengthNVT: Length of the NVT
     equilibration phase.
complexEquilSimulationMinimizationSteps: Maximum number of
     minimization steps to perform.
complexEquilSimulationProductionLength: Length of the NPT
     production phase.

Complex lambda settings:

Lambda protocol parameters for complex transformation.

complexLambdaElec: List of lambda values for electrostatics. The
     values of 0 and 1 imply state A and state B respectively.
complexLambdaRestraints: List of lambda values for restraints. The
     values of 0 and 1 imply state A and state B respectively.
complexLambdaVdw: List of lamda values for van der Waals. The
     values of of 0 and 1 imply state A and state B respectively.

Complex output settings:

Parameters controlling simulation output during final phase of
complex transformation.

complexOutputCheckpointInterval: Frequency to write the checkpoint
     file.
complexOutputCheckpointStorageFilename: Checkpoint filename.
complexOutputForcefieldCache: Filename for caching small molecule
     residue templates.
complexOutputFilename: Trajectory filename.
complexOutputIndices: Selection string for selecting coordinates to
     write.
complexOutputStructure: Topology structure filename.
complexOutputPositionsWriteFrequency: Frequency for writing
     positions to trajectory file.
complexOutputVelocitiesWriteFrequency: Frequency for writing
     velocities to trajectory file.

Complex simulation settings:

Parameters controlling simulation during final phase of complex
transformation.

complexSimulationEarlyTerminationTargetError: Target error for the
     real time analysis measured in kcal/mol. Once the MBAR error of
     the free energy is at or below this value, the simulation will
     be considered complete. The suggested value of 0.12 has shown to
     be effective in both hydration and binding free energy
     benchmarks.
complexSimulationEquilibrationLength: Length of the equilibration
     phase. The specified value must be divisible by
     'integratorTimestep'.
complexSimulationMinimizationSteps: Maximum number of minimization
     steps to perform.
complexSimulationNReplicas: Number of replicas to use.
complexSimulationProductionLength: Length of the production phase.
     The specified value must be divisible by 'integratorTimestep'.
complexSimulationRealTimeAnalysisMinimumTime: Time interval for
     performing analysis of the free energies. At each interval, real
     time analysis data will be written to a yaml file named
     <outputFileName>_real_time_analysis.yaml. The current error
     in the estimate will also be assessed and the simulation will
     be terminated when it drops below
     'complexSimulationEarlyTerminationTargetError'.
complexSimulationSamplerMethod: Alchemical sampling method to use:
     REPEX (Hamiltonian REPlica EXchange), SAMS (Self-Adjusted
     Mixture Sampling), or Independent (Independently sampled lambda
     windows).
complexSimulationSamsFlatnessCriteria:Method for assessing when to
     switch to asymptomatically optimal scheme for SAMS.
complexSimulationsamsGamma0: Initial weight adaptation rate for
     SAMS.
complexSimulationTimePerIteration: Simulation time between each MCMC move attempt

Complex solvation settings:

Solvation parameters for the system, including the solvent model and
the solvent padding.

complexSolvationBoxShape: Shape of the periodic solvent box.
complexSolvationBoxSize: Lengths of the unit cell for a solvent box.
complexSolvationSolventModel: Forcefield water model to use during
     solvation and defining the model properties.
complexSolvationSolventPadding: Minimum distance from any solute
     bounding sphere to the edge of the box.

Engine settings:

Parameters configuring the compute platform used by the OpenMM to
perform the simulation.

engineComputePlatform: Platform to use for running OpenMM MD
     calculations.
engineGpuDeviceIndex: Space delimited list of device indices
     to use for running OpenMM MD calculations.

Forcefield settings:

forcefieldConstraints:Constraints to use.
forcefields: List of valid forcefield paths for all components
     except small molecules.
forcefieldHydrogenMass: Mass to be repartitioned to hydrogens
     from neighboring heavy atoms.
forcefieldNonbondedCutoff: Cutoff for short range nonbonded
     interactions.
forcefieldNonbondedMethod: Method for treating nonbonded
     interactions.
forcefieldRigidWater: Use a rigid water model.
forcefieldSmallMoleculeForcefield: A valid forcefield name to use
     for small molecules.

Integrator settings:

Parameters controlling the LangevinSplittingDynamicsMove integrator
used for simulation.

integratorBarostatFrequency: Frequency at which volume scaling
     changes should be attempted.
integratorConstraintTolerance: Tolerance for constraint solver.
integratorLangevinCollisionRate: Collision frequency.
integratorNRestartAttempts: Number of attempts to restart from
     Context in case there are NaNs in the energies after
     integration.
integratorReassignVelocities: Reassign velocities from the
     Maxwell-Boltzmann distribution at the beginning of each
     Monte Carlo move.
integratorRemoveCom: Remove the center of mass motion.
integratorTimestep: Size of the simulation timestep.

Partial charge settings:

Parameters for automatically assigning missing partial charges to
small molecules, including the partial charge method.

partialChargeNaglModel: Model to use for partial charge assignment.
     A value of None implies the use of the latest available
     production AM1BCC model.
partialChargeNumberOfConformers: Number of conformers to generate
     as part of the partial charge assignment. A value of None
     implies the use of the existing conformer.
partialChargeOffToolkitBackend: OpenFF toolkit registry backend to
     use for calculating partial charges.
partialChargeMethod: Method to use for calculating partial charges.

Restraint settings:

Parameters to configure Boresch-style restraint between two groups
of atoms named host (Hx) and guest (Gx).

restraintKPhiA: Equilibrium force constant for the dihedral formed
     by H2-H1-H0-G0.
restraintKPhiB: Equilibrium force constant for the dihedral formed
     by H1-H0-G0-G1.
restraintKPhiC: Equilibrium force constant for the dihedral formed
     by H0-G0-G1-G2.
restraintKR: Bond spring constant between H0 and G0.
restraintKThetaA: Spring constant for the angle formed by H1-H0-G0.
restraintKThetaB: Spring constant for the angle formed by H0-G0-G1
restraintAnchorFindingStrategy: Boresch atom picking strategy to
     use. bonded: pick host atoms that are bonded to each other.
restraintDsspFilter: Apply DSSP filter to the host atoms.
     multi-residue: pick host atoms which can span multiple
     residues.
restraintHostMaxDistance: Minimum distance between any host atom
     and the guest G0 atom.
restraintHostMinDistance: Xaximum distance between any host atom
     and the guest G0 atom
restraintHostSelection: A valid selection string to sub-select the
     host atoms which will be involved in the restraint.
restraintRmsfCutoff: Cutoff value for filtering atoms by their root
     mean square fluctuation. Atoms with values above this cutoff
     are ignored.

Solvent equil output settings:
Solvent_equil_simulation_settings:
Solvent lambda settings:
Solvent output settings:
Solvent simulation settings:
Solvent solvation settings:

The solvent settings are similar to the complex settings already
described under various sections for complex. The prefix 'solvent'
is used for the names of the pramaters instead of the prefix
'complex.'

Thermo settings:

Thermodynamic parameters, including the temperature and the pressure
of the system.

thermoPh: Simulation pH
thermoPressure: Simulation pressure.
thermoRedoxPotential:Simulation redox potential.
thermoTemperature: Simulation temperature.

-e, --examples

Print examples.

--executeDAGParams <Name,Value,..> [default: auto]

A comma delimited list of parameter name and value pairs for executing protocol DAGs (Directed Acyclic Graph) to run ABFE calculations.

The supported parameter names along with their default values are are shown below:

keepShared, yes [ Possible values: yes or no ]
keepScratch, no [ Possible values: yes or no ]
nRetries, 2 [ Possible values: >= 0. A value of 0 implies only
     1 try. ]

A brief description of parameters is provided below:

keepShared: Keep shared directories after the execution of DAG.
keepScratch: Keep scratch directories after the execution of DAG.
nRetries: Number of times to attempt the execution.

-h, --help

Print this help message.

-i, --infile <infile>

Input file name containing a macromolecule.

-l, --list

List default ABFE protocol settings provided by OpenFE module AbsoluteBindingProtocol.

--loggingLevel <Info, Warning or Error> [default: Error]

Logging level to configure the 'root logger' via logging.basicConfig() function. The default logging level is changed from 'logging.INFO' to 'logging.ERROR'. Otherwise, OpenFE and its associated modules may generate a lot of informational messages.

-m, --mode <FirstMolecule, AllMolecules, or ...> [default: FirstMolecule]

Calculate ABFE for the first molecule, the specified molecule names, or all molecules in an input file. Possible values: FirstMolecule, AllMolecules, or MoleculeNames. You must specify a comma delimited list of molecule names using '--moleculeNames'option during 'MoleculeNames' value for '--mode' option.

--missingChargeMode <Calculate or Stop> [default: Stop]

Calculate missing partial charges for molecules before running ABFE calculations or terminate the execution of the script. The missing partial charges will be automatically calculated by OpenFE module AbsoluteBindingProtocol during the calculation of ABFE. You may control the calculation of partial charges by specifying values for partialCharge* parameters using '--abfe' option.

--moleculeNames <MolName1,MolName2,..>

A comma delimited list of molecule names for calculating ABFEs. This option is only used during 'MoleculeNames' value for '--mode' option.

-o, --outfileDir <outfiledir>

Output directory.

--outfilePrefix <text> [default: auto]

Prefix for generating output files under output directory.

--overwrite

Overwrite existing files.

--resultFileParams <Name,Value,..> [default: auto]

A comma delimited list of parameter name and value pairs for writing calculated RHFEs values to a results file.

The supported parameter names along with their default values are are shown below:

precision, 4 [ Possible values: > 0 ]
delimiter, comma [ Possible values: comma or tab ]

--solventParams <Name,Value,...> [default: auto]

A comma delimited list of parameter name and value pairs for solvent component. You must specify valid OpenFE values. No extensive validation is performed. These parameters are used in conjunction with solvation* parameters available through '--abfeParams' to perform solvation.

The supported parameter names along with their default values are are shown below:

positiveIon, Na+ [ Possible value: Li+, Na+, K+, Rb+, or Cs+ ]
negativeIon, Cl- [ Possible values: Cl-, Br-, F-, or I- ]
neutralize, yes [ Possible values: yes or no ]
ionConcentration, 0.15 [ Units: molar ]

A brief description of parameters is provided below:

positiveIon, negativeion: Pair of ions used to neutralize and bring
     the solvent to required ionic concentration.
neutralize: Neutralize the net charge on the chemical state by the
     ions in the solvent component.
ionConcentration: Ionic concentration.

-s, --smallMolFile <SmallMolFile>

Input file containing small molecules.

--smallMolFileParams <Name,Value,...> [default: auto]

A comma delimited list of parameter name and value pairs for reading molecules from files. The supported parameter names for different file formats, along with their default values, are shown below:

SD: removeHydrogens,no,sanitize,yes,strictParsing,yes

-w, --workingdir <dir>

Location of working directory which defaults to the current directory.

EXAMPLES

The sample protein and ligand files for tyrosine kinase 2 (Tyk2) are distributed with MayaChemTools and are available in data directory. These files have been taken from OpenFE distribution for example notebooks. The AM1BCC partial charges been calculated for the ligands in SD file to facilitate calculations. You may review OpenFE tutorial notebooks for the expected results.

To calcuate ABFE for the first molecule in a SD file, performing 3 independent repeats of the entire MD sampling process to estimate ABFE for the molecule, each solvent and vacuum MD repeat consisting of equilibration phase ( Complex: Minimization - 5,000; NVT - 0.25 ns; NPT - 0.5; NPT prod - 5.0 ns; Solvent: Minimization - 5,000; NVT - 0.1; NPT - 0.2 ns; NPT prod - 0.5 ns) and production phase ( Complex: Minimization - 5,000; NPT equil - 1.0 ns; NPT prod: 10.0 ns; Solvent: Minimization - 5,000; NPT equil - 1.0 ns; NPT prod - 10 ns) using a step size of of 4 fs, writing out appropriate trajectory and PDB files for each MD repeat in Results subdirectory under output directory, type:

To run the first example for calculating ABFE for specific molecules using CUDA platform on your machine to perform solvent and vacuum MD simulations and generate various output files, type:

To run the second example to see all warning messages produced by OpenFE modules and write various output files, type;

To run the first example for calculating ABFE for all molecules using CUDA platform on your machine to perform solvent and vacuum MD simulations, automatically calculate missing partial charges for molecules, and generate various output files, type:

To run the second example by specifying explict values for various parametres and generate various output files, type:

AUTHOR

Manish Sud

SEE ALSO

OpenFECalculateAbsoluteHydrationFreeEnergy.py, OpenFECalculatePartialCharges.py, OpenFECalculateRelativeBindingFreeEnergy.py, OpenFECalculateRelativeHydrationFreeEnergy.py, OpenFEGenerateLigandNetwork.py

COPYRIGHT

Copyright (C) 2025 Manish Sud. All rights reserved.

The functionality available in this script is implemented using OpenMM, an open source molecuar for alchemical free energy calculations.

This file is part of MayaChemTools.

MayaChemTools is free software; you can redistribute it and/or modify it under the terms of the GNU Lesser General Public License as published by the Free Software Foundation; either version 3 of the License, or (at your option) any later version.