def build_softcore_system(reference_system,
receptor_atoms,
ligand_atoms,
valence_lambda,
coulomb_lambda,
vdw_lambda,
annihilate=False):
"""
Build alchemically-modified system where ligand is decoupled or annihilated using *SoftcoreForce classes.
"""
# Create new system.
system = openmm.System()
# Set periodic box vectors.
[a, b, c] = reference_system.getDefaultPeriodicBoxVectors()
system.setDefaultPeriodicBoxVectors(a, b, c)
# Add atoms.
for atom_index in range(reference_system.getNumParticles()):
mass = reference_system.getParticleMass(atom_index)
system.addParticle(mass)
# Add constraints
for constraint_index in range(reference_system.getNumConstraints()):
[iatom, jatom,
r0] = reference_system.getConstraintParameters(constraint_index)
system.addConstraint(iatom, jatom, r0)
# Perturb force terms.
for force_index in range(reference_system.getNumForces()):
reference_force = reference_system.getForce(force_index)
# Dispatch forces
if isinstance(reference_force, openmm.HarmonicBondForce):
# HarmonicBondForce
force = openmm.HarmonicBondForce()
for bond_index in range(reference_force.getNumBonds()):
# Retrieve parameters.
[iatom, jatom, r0,
K] = reference_force.getBondParameters(bond_index)
# Annihilate if directed.
if annihilate and (iatom
in ligand_atoms) and (jatom
in ligand_atoms):
K *= valence_lambda
# Add bond parameters.
force.addBond(iatom, jatom, r0, K)
# Add force to new system.
system.addForce(force)
elif isinstance(reference_force, openmm.HarmonicAngleForce):
# HarmonicAngleForce
force = openmm.HarmonicAngleForce()
for angle_index in range(reference_force.getNumAngles()):
# Retrieve parameters.
[iatom, jatom, katom, theta0,
Ktheta] = reference_force.getAngleParameters(angle_index)
# Annihilate if directed:
if annihilate and (iatom in ligand_atoms) and (
jatom in ligand_atoms) and (katom in ligand_atoms):
Ktheta *= valence_lambda
# Add parameters.
force.addAngle(iatom, jatom, katom, theta0, Ktheta)
# Add force to system.
system.addForce(force)
elif isinstance(reference_force, openmm.PeriodicTorsionForce):
# PeriodicTorsionForce
force = openmm.PeriodicTorsionForce()
for torsion_index in range(reference_force.getNumTorsions()):
# Retrieve parmaeters.
[
particle1, particle2, particle3, particle4, periodicity,
phase, k
] = reference_force.getTorsionParameters(torsion_index)
# Annihilate if directed:
if annihilate and (particle1 in ligand_atoms) and (
particle2 in ligand_atoms) and (
particle3 in ligand_atoms) and (particle4
in ligand_atoms):
k *= valence_lambda
# Add parameters.
force.addTorsion(particle1, particle2, particle3, particle4,
periodicity, phase, k)
# Add force to system.
system.addForce(force)
elif isinstance(reference_force, openmm.NonbondedForce):
# NonbondedForce
force = openmm.NonbondedSoftcoreForce()
for particle_index in range(reference_force.getNumParticles()):
# Retrieve parameters.
[charge, sigma, epsilon
] = reference_force.getParticleParameters(particle_index)
# Alchemically modify parameters.
if particle_index in ligand_atoms:
charge *= coulomb_lambda
epsilon *= vdw_lambda
# Add modified particle parameters.
force.addParticle(charge, sigma, epsilon, vdw_lambda)
else:
# Add unmodified particle parameters.
force.addParticle(charge, sigma, epsilon, 1.0)
for exception_index in range(reference_force.getNumExceptions()):
# Retrieve parameters.
[iatom, jatom, chargeprod, sigma, epsilon
] = reference_force.getExceptionParameters(exception_index)
# Alchemically modify epsilon and chargeprod.
if (iatom in ligand_atoms) and (jatom in ligand_atoms):
if annihilate:
epsilon *= vdw_lambda
chargeprod *= coulomb_lambda
# Add modified exception parameters.
force.addException(iatom, jatom, chargeprod, sigma,
epsilon, vdw_lambda)
else:
# Add unmodified exception parameters.
force.addException(iatom, jatom, chargeprod, sigma,
epsilon, 1.0)
# Set parameters.
force.setNonbondedMethod(reference_force.getNonbondedMethod())
force.setCutoffDistance(reference_force.getCutoffDistance())
force.setReactionFieldDielectric(
reference_force.getReactionFieldDielectric())
force.setEwaldErrorTolerance(
reference_force.getEwaldErrorTolerance())
# Add force to new system.
#system.addForce(force)
elif isinstance(reference_force, openmm.GBSAOBCForce):
# GBSAOBCForce
force = openmm.GBSAOBCSoftcoreForce()
force.setSolventDielectric(reference_force.getSolventDielectric())
force.setSoluteDielectric(reference_force.getSoluteDielectric())
for particle_index in range(reference_force.getNumParticles()):
# Retrieve parameters.
[charge, radius, scaling_factor
] = reference_force.getParticleParameters(particle_index)
# Alchemically modify parameters.
if particle_index in ligand_atoms:
# Scale charge and contribution to GB integrals.
force.addParticle(charge * coulomb_lambda, radius,
scaling_factor, coulomb_lambda)
else:
# Don't modulate GB.
force.addParticle(charge, radius, scaling_factor, 1.0)
# Add force to new system.
#system.addForce(force)
else:
# Don't add unrecognized forces.
pass
return system
def build_alchemically_modified_system(reference_system,
receptor_atoms,
ligand_atoms,
annihilate=True):
"""
Build alchemically-modified system where ligand is decoupled or annihilated.
"""
# Create new system.
system = openmm.System()
# Add atoms.
for atom_index in range(reference_system.getNumParticles()):
mass = reference_system.getParticleMass(atom_index)
system.addParticle(mass)
# Add constraints
for constraint_index in range(reference_system.getNumConstraints()):
[iatom, jatom,
r0] = reference_system.getConstraintParameters(constraint_index)
system.addConstraint(iatom, jatom, r0)
# Perturb force terms.
for force_index in range(reference_system.getNumForces()):
reference_force = reference_system.getForce(force_index)
# Dispatch forces
if isinstance(reference_force, openmm.HarmonicBondForce):
# HarmonicBondForce
force = openmm.HarmonicBondForce()
for bond_index in range(reference_force.getNumBonds()):
# Retrieve parameters.
[iatom, jatom, r0,
K] = reference_force.getBondParameters(bond_index)
# Annihilate if directed.
if annihilate and (iatom
in ligand_atoms) and (jatom
in ligand_atoms):
K *= 0.0
# Add bond parameters.
force.addBond(iatom, jatom, r0, K)
# Add force to new system.
system.addForce(force)
elif isinstance(reference_force, openmm.HarmonicAngleForce):
# HarmonicAngleForce
force = openmm.HarmonicAngleForce()
for angle_index in range(reference_force.getNumAngles()):
# Retrieve parameters.
[iatom, jatom, katom, theta0,
Ktheta] = reference_force.getAngleParameters(angle_index)
# Annihilate if directed:
if annihilate and (iatom in ligand_atoms) and (
jatom in ligand_atoms) and (katom in ligand_atoms):
Ktheta *= 0.0
# Add parameters.
force.addAngle(iatom, jatom, katom, theta0, Ktheta)
# Add force to system.
system.addForce(force)
elif isinstance(reference_force, openmm.PeriodicTorsionForce):
# PeriodicTorsionForce
force = openmm.PeriodicTorsionForce()
for torsion_index in range(reference_force.getNumTorsions()):
# Retrieve parmaeters.
[
particle1, particle2, particle3, particle4, periodicity,
phase, k
] = reference_force.getTorsionParameters(torsion_index)
# Annihilate if directed:
if annihilate and (particle1 in ligand_atoms) and (
particle2 in ligand_atoms) and (
particle3 in ligand_atoms) and (particle4
in ligand_atoms):
k *= 0.0
# Add parameters.
force.addTorsion(particle1, particle2, particle3, particle4,
periodicity, phase, k)
# Add force to system.
system.addForce(force)
elif isinstance(reference_force, openmm.NonbondedForce):
# NonbondedForce
force = openmm.NonbondedSoftcoreForce()
for particle_index in range(reference_force.getNumParticles()):
# Retrieve parameters.
[charge, sigma, epsilon
] = reference_force.getParticleParameters(particle_index)
# Alchemically modify parameters.
alchemical_lambda = 1.0
if particle_index in ligand_atoms:
alchemical_lambda = 0.0
charge *= 0.0
if annihilate:
epsilon *= 0.0
# Add modified particle parameters.
force.addParticle(charge, sigma, epsilon, alchemical_lambda)
for exception_index in range(reference_force.getNumExceptions()):
# Retrieve parameters.
[iatom, jatom, chargeprod, sigma, epsilon
] = reference_force.getExceptionParameters(exception_index)
# TODO: Alchemically modify parameters.
if (iatom in ligand_atoms) and (jatom in ligand_atoms):
chargeprod *= 0.0
if annihilate:
epsilon *= 0.0
# Add modified exception parameters.
force.addException(iatom, jatom, chargeprod, sigma, epsilon)
# Set parameters.
force.setNonbondedMethod(reference_force.getNonbondedMethod())
force.setCutoffDistance(reference_force.getCutoffDistance())
force.setReactionFieldDielectric(
reference_force.getReactionFieldDielectric())
force.setEwaldErrorTolerance(
reference_force.getEwaldErrorTolerance())
# Add force to new system.
system.addForce(force)
elif isinstance(reference_force, openmm.GBSAOBCForce):
# GBSAOBCForce
force = openmm.GBSAOBCSoftcoreForce()
for particle_index in range(reference_force.getNumParticles()):
# Retrieve parameters.
[charge, radius, scaling_factor
] = reference_force.getParticleParameters(particle_index)
# Alchemically modify parameters.
nonpolar_scaling_factor = 1.0
if particle_index in ligand_atoms:
charge *= 0.0
#radius *= 0.0
#scaling_factor *= 0.0
nonpolar_scaling_factor = 0.0
pass
# Add parameters.
force.addParticle(charge, radius, scaling_factor,
nonpolar_scaling_factor)
force.setSolventDielectric(reference_force.getSolventDielectric())
force.setSoluteDielectric(reference_force.getSoluteDielectric())
#force.setCutoffDistance( reference_force.getCutoffDistance() )
#force.setNonbondedMethod( reference_force.getNonbondedMethod() )
# Add force to new system.
system.addForce(force)
else:
# Don't add unrecognized forces.
pass
return system