def createSystem():
protomsdir = "%s/Work/ProtoMS" % os.getenv("HOME")
protoms = ProtoMS("%s/protoms2" % protomsdir)
protoms.addParameterFile("%s/parameter/amber99.ff" % protomsdir)
protoms.addParameterFile("%s/parameter/solvents.ff" % protomsdir)
protoms.addParameterFile("%s/parameter/gaff.ff" % protomsdir)
protoms.addParameterFile(solute_params)
solute = PDB().readMolecule(solute_file)
solute = solute.edit().rename(solute_name).commit()
solute = protoms.parameterise(solute, ProtoMS.SOLUTE)
perturbation = solute.property("perturbations")
lam = Symbol("lambda")
lam_fwd = Symbol("lambda_{fwd}")
lam_bwd = Symbol("lambda_{bwd}")
initial = Perturbation.symbols().initial()
final = Perturbation.symbols().final()
solute = solute.edit().setProperty(
"perturbations",
perturbation.recreate((1 - lam) * initial + lam * final)).commit()
solute_fwd = solute.edit().renumber().setProperty(
"perturbations", perturbation.substitute(lam, lam_fwd)).commit()
solute_bwd = solute.edit().renumber().setProperty(
"perturbations", perturbation.substitute(lam, lam_bwd)).commit()
solvent = PDB().read(solvent_file)
tip4p = solvent.moleculeAt(0).molecule()
tip4p = tip4p.edit().rename(solvent_name).commit()
tip4p = protoms.parameterise(tip4p, ProtoMS.SOLVENT)
tip4p_chgs = tip4p.property("charge")
tip4p_ljs = tip4p.property("LJ")
for i in range(0, solvent.nMolecules()):
tip4p = solvent.moleculeAt(i).molecule()
tip4p = tip4p.edit().rename(solvent_name) \
.setProperty("charge", tip4p_chgs) \
.setProperty("LJ", tip4p_ljs) \
.commit()
solvent.update(tip4p)
system = System()
solutes = MoleculeGroup("solutes")
solutes.add(solute)
solutes.add(solute_fwd)
solutes.add(solute_bwd)
solvent = MoleculeGroup("solvent", solvent)
all = MoleculeGroup("all")
all.add(solutes)
all.add(solvent)
system.add(solutes)
system.add(solvent)
system.add(all)
solventff = InterCLJFF("solvent:solvent")
solventff.add(solvent)
solute_intraff = InternalFF("solute_intraff")
solute_intraff.add(solute)
solute_fwd_intraff = InternalFF("solute_fwd_intraff")
solute_fwd_intraff.add(solute_fwd)
solute_bwd_intraff = InternalFF("solute_bwd_intraff")
solute_bwd_intraff.add(solute_bwd)
solute_intraclj = IntraCLJFF("solute_intraclj")
solute_intraclj.add(solute)
solute_fwd_intraclj = IntraCLJFF("solute_fwd_intraclj")
solute_fwd_intraclj.add(solute_fwd)
solute_bwd_intraclj = IntraCLJFF("solute_bwd_intraclj")
solute_bwd_intraclj.add(solute_bwd)
solute_solventff = InterGroupCLJFF("solute:solvent")
solute_solventff.add(solute, MGIdx(0))
solute_solventff.add(solvent, MGIdx(1))
solute_fwd_solventff = InterGroupCLJFF("solute_fwd:solvent")
solute_fwd_solventff.add(solute_fwd, MGIdx(0))
solute_fwd_solventff.add(solvent, MGIdx(1))
solute_bwd_solventff = InterGroupCLJFF("solute_bwd:solvent")
solute_bwd_solventff.add(solute_bwd, MGIdx(0))
solute_bwd_solventff.add(solvent, MGIdx(1))
forcefields = [
solventff, solute_intraff, solute_intraclj, solute_solventff,
solute_fwd_intraff, solute_fwd_intraclj, solute_fwd_solventff,
solute_bwd_intraff, solute_bwd_intraclj, solute_bwd_solventff
]
for forcefield in forcefields:
system.add(forcefield)
xsc_line = open(solvent_file, "r").readlines()[0]
words = xsc_line.split()
#HEADER box -12.5 -12.5 -12.5 12.5 12.5 12.5
space = PeriodicBox(
Vector(float(words[2]), float(words[3]), float(words[4])),
Vector(float(words[5]), float(words[6]), float(words[7])))
system.setProperty("space", space)
system.setProperty(
"switchingFunction",
HarmonicSwitchingFunction(coulomb_cutoff, coulomb_feather, lj_cutoff,
lj_feather))
system.setProperty("combiningRules", VariantProperty(combining_rules))
e_total = system.totalComponent()
e_fwd = Symbol("E_{fwd}")
e_bwd = Symbol("E_{bwd}")
total_nrg = solventff.components().total() + \
solute_intraclj.components().total() + solute_intraff.components().total() + \
solute_solventff.components().total()
fwd_nrg = solventff.components().total() + \
solute_fwd_intraclj.components().total() + solute_fwd_intraff.components().total() + \
solute_fwd_solventff.components().total()
bwd_nrg = solventff.components().total() + \
solute_bwd_intraclj.components().total() + solute_bwd_intraff.components().total() + \
solute_bwd_solventff.components().total()
system.setComponent(e_total, total_nrg)
system.setComponent(e_fwd, fwd_nrg)
system.setComponent(e_bwd, bwd_nrg)
system.setConstant(lam, 0.0)
system.setConstant(lam_fwd, 0.0)
system.setConstant(lam_bwd, 0.0)
system.add(SpaceWrapper(Vector(0, 0, 0), all))
system.add(PerturbationConstraint(solutes))
system.add(ComponentConstraint(lam_fwd, Min(lam + delta_lambda, 1)))
system.add(ComponentConstraint(lam_bwd, Max(lam - delta_lambda, 0)))
de_fwd = Symbol("de_fwd")
de_bwd = Symbol("de_bwd")
system.setComponent(de_fwd, fwd_nrg - total_nrg)
system.setComponent(de_bwd, total_nrg - bwd_nrg)
system.add("total_energy", MonitorComponent(e_total, Average()))
system.add("de_fwd",
MonitorComponent(de_fwd, FreeEnergyAverage(temperature)))
system.add("de_bwd",
MonitorComponent(de_bwd, FreeEnergyAverage(temperature)))
system.setComponent(lam, 0.0)
print "LAMBDA=0 : Energy = %f kcal mol-1" % system.energy().to(
kcal_per_mol)
print " (%f, %f)" % (system.energy(e_fwd).to(kcal_per_mol),
system.energy(e_bwd).to(kcal_per_mol))
system.setComponent(lam, 0.5)
print "LAMBDA=0.5 : Energy = %f kcal mol-1" % system.energy().to(
kcal_per_mol)
print " (%f, %f)" % (system.energy(e_fwd).to(kcal_per_mol),
system.energy(e_bwd).to(kcal_per_mol))
system.setComponent(lam, 1.0)
print "LAMBDA=1.0 : Energy = %f kcal mol-1" % system.energy().to(
kcal_per_mol)
print " (%f, %f)" % (system.energy(e_fwd).to(kcal_per_mol),
system.energy(e_bwd).to(kcal_per_mol))
return system
def loadQMMMSystem():
"""This function is called to set up the system. It sets everything
up, then returns a System object that holds the configured system"""
print("Loading the system...")
t = QTime()
if os.path.exists(s3file.val):
print("Loading existing s3 file %s..." % s3file.val)
loadsys = Sire.Stream.load(s3file.val)
else:
print("Loading from Amber files %s / %s..." %
(topfile.val, crdfile.val))
# Add the name of the ligand to the list of solute molecules
sys_scheme = NamingScheme()
sys_scheme.addSoluteResidueName(ligand_name.val)
# Load up the system. This will automatically find the protein, solute, water, solvent
# and ion molecules and assign them to different groups
loadsys = createSystem(topfile.val, crdfile.val, sys_scheme)
ligand_mol = findMolecule(loadsys, ligand_name.val)
if ligand_mol is None:
print(
"Cannot find the ligand (%s) in the set of loaded molecules!" %
ligand_name.val)
sys.exit(-1)
# Center the system with the ligand at (0,0,0)
loadsys = centerSystem(loadsys, ligand_mol)
ligand_mol = loadsys[ligand_mol.number()][0].molecule()
if reflection_radius.val is None:
loadsys = addFlexibility(loadsys, naming_scheme=sys_scheme)
else:
loadsys = addFlexibility(loadsys,
Vector(0),
reflection_radius.val,
naming_scheme=sys_scheme)
Sire.Stream.save(loadsys, s3file.val)
ligand_mol = findMolecule(loadsys, ligand_name.val)
if ligand_mol is None:
print("Cannot find the ligand (%s) in the set of loaded molecules!" %
ligand_name.val)
sys.exit(-1)
# Now build the QM/MM system
system = System("QMMM system")
if loadsys.containsProperty("reflection center"):
reflect_center = loadsys.property("reflection center").toVector()[0]
reflect_radius = float(
str(loadsys.property("reflection sphere radius")))
system.setProperty("reflection center",
AtomCoords(CoordGroup(1, reflect_center)))
system.setProperty("reflection sphere radius",
VariantProperty(reflect_radius))
space = Cartesian()
else:
space = loadsys.property("space")
if loadsys.containsProperty("average solute translation delta"):
system.setProperty("average solute translation delta", \
loadsys.property("average solute translation delta"))
if loadsys.containsProperty("average solute rotation delta"):
system.setProperty("average solute rotation delta", \
loadsys.property("average solute rotation delta"))
# create a molecule group to hold all molecules
all_group = MoleculeGroup("all")
# create a molecule group for the ligand
ligand_group = MoleculeGroup("ligand")
ligand_group.add(ligand_mol)
all_group.add(ligand_mol)
groups = []
groups.append(ligand_group)
# pull out the groups that we want from the two systems
# create a group to hold all of the fixed molecules in the bound leg
fixed_group = MoleculeGroup("fixed_molecules")
if MGName("fixed_molecules") in loadsys.mgNames():
fixed_group.add(loadsys[MGName("fixed_molecules")])
if save_pdb.val:
# write a PDB of the fixed atoms in the bound and free legs
if not os.path.exists(outdir.val):
os.makedirs(outdir.val)
PDB().write(fixed_group, "%s/fixed.pdb" % outdir.val)
# create a group to hold all of the mobile solute molecules
mobile_solutes_group = MoleculeGroup("mobile_solutes")
if MGName("mobile_solutes") in loadsys.mgNames():
mobile_solutes_group.add(loadsys[MGName("mobile_solutes")])
mobile_solutes_group.remove(ligand_mol)
if mobile_solutes_group.nMolecules() > 0:
all_group.add(mobile_solutes_group)
groups.append(mobile_solutes_group)
# create a group to hold all of the mobile solvent molecules
mobile_solvents_group = MoleculeGroup("mobile_solvents")
if MGName("mobile_solvents") in loadsys.mgNames():
mols = loadsys[MGName("mobile_solvents")]
for molnum in mols.molNums():
solvent_mol = mols[molnum][0].molecule()
mobile_solvents_group.add(solvent_mol)
all_group.add(mobile_solvents_group)
print("The number of mobile solvent molecules is %d." %
mobile_solvents_group.nMolecules())
groups.append(mobile_solvents_group)
# create the groups to hold all of the protein molecules. We will use "extract" to
# pull out only those protein atoms that are in the mobile region
protein_intra_group = MoleculeGroup("protein_intra_group")
mobile_proteins_group = MoleculeGroup("proteins")
mobile_protein_sidechains_group = MoleculeGroup("mobile_sidechains")
mobile_protein_backbones_group = MoleculeGroup("mobile_backbones")
if MGName("protein_sidechains") in loadsys.mgNames() or \
MGName("protein_backbones") in loadsys.mgNames():
all_proteins = Molecules()
try:
protein_sidechains = loadsys[MGName("protein_sidechains")]
all_proteins.add(protein_sidechains.molecules())
except:
protein_sidechains = MoleculeGroup()
try:
protein_backbones = loadsys[MGName("protein_backbones")]
all_proteins.add(protein_backbones.molecules())
except:
protein_backbones = MoleculeGroup()
try:
boundary_molecules = loadsys[MGName("boundary_molecules")]
all_proteins.add(boundary_molecules.molecules())
except:
boundary_molecules = MoleculeGroup()
for molnum in all_proteins.molNums():
protein_mol = Molecule.join(all_proteins[molnum])
if protein_mol.selectedAll():
protein_intra_group.add(protein_mol)
all_group.add(protein_mol)
mobile_protein = []
if protein_sidechains.contains(molnum):
sidechains = protein_sidechains[molnum]
for sidechain in sidechains:
mobile_protein_sidechains_group.add(sidechain)
mobile_protein += sidechains
if protein_backbones.contains(molnum):
backbones = protein_backbones[molnum]
for backbone in backbones:
mobile_protein_backbones_group.add(backbone)
mobile_protein += backbones
if len(mobile_protein) > 0:
mobile_proteins_group.add(Molecule.join(mobile_protein))
else:
# only some of the atoms have been selected. We will extract
# the mobile atoms and will then update all of the other selections
print("Extracting the mobile atoms of protein %s" %
protein_mol.molecule())
new_protein_mol = protein_mol.extract()
print("Extracted %d mobile atoms from %d total atoms..." % \
(new_protein_mol.nAtoms(), protein_mol.molecule().nAtoms()))
protein_intra_group.add(new_protein_mol)
all_group.add(new_protein_mol)
mobile_protein_view = new_protein_mol.selection()
mobile_protein_view = mobile_protein_view.selectNone()
if protein_sidechains.contains(molnum):
sidechains = protein_sidechains[molnum]
for sidechain in sidechains:
view = new_protein_mol.selection()
view = view.selectNone()
for atomid in sidechain.selection().selectedAtoms():
atom = protein_mol.atom(atomid)
resatomid = ResAtomID(atom.residue().number(),
atom.name())
view = view.select(resatomid)
mobile_protein_view = mobile_protein_view.select(
resatomid)
if view.nSelected() > 0:
mobile_protein_sidechains_group.add(
PartialMolecule(new_protein_mol, view))
if protein_backbones.contains(molnum):
backbones = protein_backbones[molnum]
for backbone in backbones:
view = new_protein_mol.selection()
view = view.selectNone()
for atomid in backbone.selection().selectedAtoms():
atom = protein_mol.atom(atomid)
resatomid = ResAtomID(atom.residue().number(),
atom.name())
view = view.select(resatomid)
mobile_protein_view = mobile_protein_view.select(
resatomid)
if view.nSelected() > 0:
mobile_protein_backbones_group.add(
PartialMolecule(new_protein_mol, view))
print("Number of moved protein sidechain residues = %s" %
mobile_protein_sidechains_group.nViews())
print("Number of moved protein backbone residues = %s" %
mobile_protein_backbones_group.nViews())
if mobile_protein_view.nSelected() > 0:
mobile_proteins_group.add(
PartialMolecule(new_protein_mol, mobile_protein_view))
groups.append(mobile_protein_backbones_group)
groups.append(mobile_protein_sidechains_group)
groups.append(all_group)
# finished added in all of the proteins
for group in groups:
if group.nMolecules() > 0:
print("Adding group %s" % group.name())
system.add(group)
# now add in the forcefields for the system...
print("Creating the forcefields for the QM/MM system...")
# first, group together the molecules grouped above into convenient
# groups for the forcefields
# group holding just the ligand
ligand_mols = ligand_group.molecules()
# group holding all of the mobile atoms
mobile_mols = mobile_solvents_group.molecules()
mobile_mols.add(mobile_solutes_group.molecules())
mobile_mols.add(protein_intra_group.molecules())
# group holding all of the mobile atoms in the bound leg, excluding the
# buffer atoms that are fixed, but bonded to mobile atoms
mobile_buffered_mols = mobile_solvents_group.molecules()
mobile_buffered_mols.add(mobile_solutes_group.molecules())
mobile_buffered_mols.add(mobile_proteins_group.molecules())
# group holding all of the protein molecules that need intramolecular terms calculated
protein_intra_mols = protein_intra_group.molecules()
# group holding all of the solute molecules that nede intramolecular terms calculated
solute_intra_mols = mobile_solutes_group.molecules()
forcefields = []
###
### INTRA-ENERGY OF THE LIGAND AND CLUSTER
###
# intramolecular energy of the ligand
ligand_intraclj = IntraCLJFF("ligand:intraclj")
ligand_intraclj = setCLJProperties(ligand_intraclj, space)
ligand_intraclj.add(ligand_mols)
ligand_intraff = InternalFF("ligand:intra")
ligand_intraff.add(ligand_mols)
forcefields.append(ligand_intraclj)
forcefields.append(ligand_intraff)
ligand_mm_nrg = ligand_intraclj.components().total(
) + ligand_intraff.components().total()
###
### FORCEFIELDS INVOLVING THE LIGAND/CLUSTER AND OTHER ATOMS
###
# forcefield holding the energy between the ligand and the mobile atoms in the
# bound leg
ligand_mobile = InterGroupCLJFF("system:ligand-mobile")
ligand_mobile = setCLJProperties(ligand_mobile, space)
ligand_mobile.add(ligand_mols, MGIdx(0))
ligand_mobile.add(mobile_mols, MGIdx(1))
qm_ligand = QMMMFF("system:ligand-QM")
qm_ligand.add(ligand_mols, MGIdx(0))
qm_ligand = setQMProperties(qm_ligand, space)
zero_energy = 0
if not intermolecular_only.val:
if qm_zero_energy.val is None:
# calculate the delta value for the system - this is the difference between
# the MM and QM intramolecular energy of the ligand
t.start()
print("\nComparing the MM and QM energies of the ligand...")
mm_intra = ligand_intraclj.energy().value(
) + ligand_intraff.energy().value()
print("MM energy = %s kcal mol-1 (took %s ms)" %
(mm_intra, t.elapsed()))
t.start()
zero_sys = System()
zero_sys.add(qm_ligand)
qm_intra = zero_sys.energy().value()
print("QM energy = %s kcal mol-1 (took %s ms)" %
(qm_intra, t.elapsed()))
print("\nSetting the QM zero energy to %s kcal mol-1" %
(qm_intra - mm_intra))
qm_ligand.setZeroEnergy((qm_intra - mm_intra) * kcal_per_mol)
zero_energy = qm_intra - mm_intra
else:
print("\nManually setting the QM zero energy to %s" %
qm_zero_energy.val)
qm_ligand.setZeroEnergy(qm_zero_energy.val)
zero_energy = qm_zero_energy.val
qm_ligand.add(mobile_mols, MGIdx(1))
ligand_mm_nrg += ligand_mobile.components().total()
ligand_qm_nrg = qm_ligand.components().total() + ligand_mobile.components(
).lj()
if intermolecular_only.val:
# the QM model still uses the MM intramolecular energy of the ligand
ligand_qm_nrg += ligand_intraclj.components().total(
) + ligand_intraff.components().total()
forcefields.append(ligand_mobile)
forcefields.append(qm_ligand)
if fixed_group.nMolecules() > 0:
# there are fixed molecules
# Whether or not to disable the grid and calculate all energies atomisticly
if disable_grid:
# we need to renumber all of the fixed molecules so that they don't clash
# with the mobile molecules
print("Renumbering fixed molecules...")
fixed_group = renumberMolecules(fixed_group)
# forcefield holding the energy between the ligand and the fixed atoms in the bound leg
if disable_grid:
ligand_fixed = InterGroupCLJFF("system:ligand-fixed")
ligand_fixed = setCLJProperties(ligand_fixed, space)
ligand_fixed = setFakeGridProperties(ligand_fixed, space)
ligand_fixed.add(ligand_mols, MGIdx(0))
ligand_fixed.add(fixed_group, MGIdx(1))
qm_ligand.add(fixed_group, MGIdx(1))
ligand_mm_nrg += ligand_fixed.components().total()
ligand_qm_nrg += ligand_fixed.components().lj()
forcefields.append(ligand_fixed)
else:
ligand_fixed = GridFF2("system:ligand-fixed")
ligand_fixed = setCLJProperties(ligand_fixed, space)
ligand_fixed = setGridProperties(ligand_fixed)
ligand_fixed.add(ligand_mols, MGIdx(0))
ligand_fixed.addFixedAtoms(fixed_group)
qm_ligand.addFixedAtoms(fixed_group)
ligand_mm_nrg += ligand_fixed.components().total()
ligand_qm_nrg += ligand_fixed.components().lj()
forcefields.append(ligand_fixed)
###
### FORCEFIELDS NOT INVOLVING THE LIGAND
###
# forcefield holding the intermolecular energy between all molecules
mobile_mobile = InterCLJFF("mobile-mobile")
mobile_mobile = setCLJProperties(mobile_mobile, space)
mobile_mobile.add(mobile_mols)
other_nrg = mobile_mobile.components().total()
forcefields.append(mobile_mobile)
# forcefield holding the energy between the mobile atoms and
# the fixed atoms
if disable_grid.val:
mobile_fixed = InterGroupCLJFF("mobile-fixed")
mobile_fixed = setCLJProperties(mobile_fixed)
mobile_fixed = setFakeGridProperties(mobile_fixed, space)
mobile_fixed.add(mobile_buffered_mols, MGIdx(0))
mobile_fixed.add(fixed_group, MGIdx(1))
other_nrg += mobile_fixed.components().total()
forcefields.append(mobile_fixed)
else:
mobile_fixed = GridFF2("mobile-fixed")
mobile_fixed = setCLJProperties(mobile_fixed, space)
mobile_fixed = setGridProperties(mobile_fixed)
# we use mobile_buffered_group as this group misses out atoms that are bonded
# to fixed atoms (thus preventing large energies caused by incorrect non-bonded calculations)
mobile_fixed.add(mobile_buffered_mols, MGIdx(0))
mobile_fixed.addFixedAtoms(fixed_group)
other_nrg += mobile_fixed.components().total()
forcefields.append(mobile_fixed)
# intramolecular energy of the protein
if protein_intra_mols.nMolecules() > 0:
protein_intraclj = IntraCLJFF("protein_intraclj")
protein_intraclj = setCLJProperties(protein_intraclj, space)
protein_intraff = InternalFF("protein_intra")
for molnum in protein_intra_mols.molNums():
protein_mol = Molecule.join(protein_intra_mols[molnum])
protein_intraclj.add(protein_mol)
protein_intraff.add(protein_mol)
other_nrg += protein_intraclj.components().total()
other_nrg += protein_intraff.components().total()
forcefields.append(protein_intraclj)
forcefields.append(protein_intraff)
# intramolecular energy of any other solutes
if solute_intra_mols.nMolecules() > 0:
solute_intraclj = IntraCLJFF("solute_intraclj")
solute_intraclj = setCLJProperties(solute_intraclj, space)
solute_intraff = InternalFF("solute_intra")
for molnum in solute_intra_mols.molNums():
solute_mol = Molecule.join(solute_intra_mols[molnum])
solute_intraclj.add(solute_mol)
solute_intraff.add(solute_mol)
other_nrg += solute_intraclj.components().total()
other_nrg += solute_intraff.components().total()
forcefields.append(solute_intraclj)
forcefields.append(solute_intraff)
###
### NOW ADD THE FORCEFIELDS TO THE SYSTEM
###
###
### SETTING THE FORCEFIELD EXPRESSIONS
###
lam = Symbol("lambda")
e_slow = ((1 - lam) * ligand_qm_nrg) + (lam * ligand_mm_nrg) + other_nrg
e_fast = ligand_mm_nrg + other_nrg
de_by_dlam = ligand_mm_nrg - ligand_qm_nrg
for forcefield in forcefields:
system.add(forcefield)
system.setConstant(lam, 0.0)
system.setComponent(Symbol("E_{fast}"), e_fast)
system.setComponent(Symbol("E_{slow}"), e_slow)
system.setComponent(Symbol("dE/dlam"), de_by_dlam)
system.setComponent(system.totalComponent(), e_slow)
system.setProperty("space", space)
if space.isPeriodic():
# ensure that all molecules are wrapped into the space with the ligand at the center
print("Adding in a space wrapper constraint %s, %s" %
(space, ligand_mol.evaluate().center()))
system.add(SpaceWrapper(ligand_mol.evaluate().center(), all_group))
system.applyConstraints()
print("\nHere are the values of all of the initial energy components...")
t.start()
printEnergies(system.energies())
print("(these took %d ms to evaluate)\n" % t.elapsed())
# Create a monitor to monitor the free energy average
system.add("dG/dlam",
MonitorComponent(Symbol("dE/dlam"), AverageAndStddev()))
if intermolecular_only.val:
print(
"\n\n## This simulation uses QM to model *only* the intermolecular energy between"
)
print(
"## the QM and MM atoms. The intramolecular energy of the QM atoms is still"
)
print("## modelled using MM.\n")
else:
print(
"\n\n## This simulation uses QM to model both the intermolecular and intramolecular"
)
print(
"## energies of the QM atoms. Because the this, we have to adjust the 'zero' point"
)
print(
"## of the QM potential. You need to add the value %s kcal mol-1 back onto the"
% zero_energy)
print("## QM->MM free energy calculated using this program.\n")
return system
def loadQMMMSystem():
"""This function is called to set up the system. It sets everything
up, then returns a System object that holds the configured system"""
print("Loading the system...")
t = QTime()
if os.path.exists(s3file.val):
print("Loading existing s3 file %s..." % s3file.val)
loadsys = Sire.Stream.load(s3file.val)
else:
print("Loading from Amber files %s / %s..." % (topfile.val, crdfile.val))
# Add the name of the ligand to the list of solute molecules
sys_scheme = NamingScheme()
sys_scheme.addSoluteResidueName(ligand_name.val)
# Load up the system. This will automatically find the protein, solute, water, solvent
# and ion molecules and assign them to different groups
loadsys = createSystem(topfile.val, crdfile.val, sys_scheme)
ligand_mol = findMolecule(loadsys, ligand_name.val)
if ligand_mol is None:
print("Cannot find the ligand (%s) in the set of loaded molecules!" % ligand_name.val)
sys.exit(-1)
# Center the system with the ligand at (0,0,0)
loadsys = centerSystem(loadsys, ligand_mol)
ligand_mol = loadsys[ligand_mol.number()].molecule()
if reflection_radius.val is None:
loadsys = addFlexibility(loadsys, naming_scheme=sys_scheme )
else:
loadsys = addFlexibility(loadsys, Vector(0), reflection_radius.val, naming_scheme=sys_scheme)
Sire.Stream.save(loadsys, s3file.val)
ligand_mol = findMolecule(loadsys, ligand_name.val)
if ligand_mol is None:
print("Cannot find the ligand (%s) in the set of loaded molecules!" % ligand_name.val)
sys.exit(-1)
# Now build the QM/MM system
system = System("QMMM system")
if loadsys.containsProperty("reflection center"):
reflect_center = loadsys.property("reflection center").toVector()[0]
reflect_radius = float(str(loadsys.property("reflection sphere radius")))
system.setProperty("reflection center", AtomCoords(CoordGroup(1,reflect_center)))
system.setProperty("reflection sphere radius", VariantProperty(reflect_radius))
space = Cartesian()
else:
space = loadsys.property("space")
if loadsys.containsProperty("average solute translation delta"):
system.setProperty("average solute translation delta", \
loadsys.property("average solute translation delta"))
if loadsys.containsProperty("average solute rotation delta"):
system.setProperty("average solute rotation delta", \
loadsys.property("average solute rotation delta"))
# create a molecule group to hold all molecules
all_group = MoleculeGroup("all")
# create a molecule group for the ligand
ligand_group = MoleculeGroup("ligand")
ligand_group.add(ligand_mol)
all_group.add(ligand_mol)
groups = []
groups.append(ligand_group)
# pull out the groups that we want from the two systems
# create a group to hold all of the fixed molecules in the bound leg
fixed_group = MoleculeGroup("fixed_molecules")
if MGName("fixed_molecules") in loadsys.mgNames():
fixed_group.add( loadsys[ MGName("fixed_molecules") ] )
if save_pdb.val:
# write a PDB of the fixed atoms in the bound and free legs
if not os.path.exists(outdir.val):
os.makedirs(outdir.val)
PDB().write(fixed_group, "%s/fixed.pdb" % outdir.val)
# create a group to hold all of the mobile solute molecules
mobile_solutes_group = MoleculeGroup("mobile_solutes")
if MGName("mobile_solutes") in loadsys.mgNames():
mobile_solutes_group.add( loadsys[MGName("mobile_solutes")] )
mobile_solutes_group.remove(ligand_mol)
if mobile_solutes_group.nMolecules() > 0:
all_group.add(mobile_solutes_group)
groups.append(mobile_solutes_group)
# create a group to hold all of the mobile solvent molecules
mobile_solvents_group = MoleculeGroup("mobile_solvents")
if MGName("mobile_solvents") in loadsys.mgNames():
mols = loadsys[MGName("mobile_solvents")]
for molnum in mols.molNums():
solvent_mol = mols[molnum].molecule()
mobile_solvents_group.add(solvent_mol)
all_group.add(mobile_solvents_group)
print("The number of mobile solvent molecules is %d." % mobile_solvents_group.nMolecules())
groups.append(mobile_solvents_group)
# create the groups to hold all of the protein molecules. We will use "extract" to
# pull out only those protein atoms that are in the mobile region
protein_intra_group = MoleculeGroup("protein_intra_group")
mobile_proteins_group = MoleculeGroup("proteins")
mobile_protein_sidechains_group = MoleculeGroup("mobile_sidechains")
mobile_protein_backbones_group = MoleculeGroup("mobile_backbones")
if MGName("protein_sidechains") in loadsys.mgNames() or \
MGName("protein_backbones") in loadsys.mgNames():
all_proteins = Molecules()
try:
protein_sidechains = loadsys[MGName("protein_sidechains")]
all_proteins.add(protein_sidechains.molecules())
except:
protein_sidechains = MoleculeGroup()
try:
protein_backbones = loadsys[MGName("protein_backbones")]
all_proteins.add(protein_backbones.molecules())
except:
protein_backbones = MoleculeGroup()
try:
boundary_molecules = loadsys[MGName("boundary_molecules")]
all_proteins.add(boundary_molecules.molecules())
except:
boundary_molecules = MoleculeGroup()
for molnum in all_proteins.molNums():
protein_mol = all_proteins[molnum].join()
if protein_mol.selectedAll():
protein_intra_group.add(protein_mol)
all_group.add(protein_mol)
mobile_protein = None
try:
mobile_protein = protein_sidechains[molnum]
mobile_protein_sidechains_group.add( mobile_protein )
except:
pass
try:
if mobile_protein is None:
mobile_protein = protein_backbones[molnum]
mobile_protein_backbones_group.add( mobile_protein )
else:
mobile_protein.add( protein_backbones[molnum].selection() )
mobile_protein_backbones_group.add( protein_backbones[molnum] )
except:
pass
if not (mobile_protein is None):
mobile_proteins_group.add( mobile_protein.join() )
else:
# only some of the atoms have been selected. We will extract
# the mobile atoms and will then update all of the other selections
print("Extracting the mobile atoms of protein %s" % protein_mol)
new_protein_mol = protein_mol.extract()
print("Extracted %d mobile atoms from %d total atoms..." % \
(new_protein_mol.nAtoms(), protein_mol.molecule().nAtoms()))
protein_intra_group.add(new_protein_mol)
all_group.add( new_protein_mol )
mobile_protein_view = new_protein_mol.selection()
mobile_protein_view = mobile_protein_view.selectNone()
try:
sidechains = protein_sidechains[molnum]
for i in range(0,sidechains.nViews()):
view = new_protein_mol.selection()
view = view.selectNone()
for atomid in sidechains.viewAt(i).selectedAtoms():
atom = protein_mol.atom(atomid)
resatomid = ResAtomID( atom.residue().number(), atom.name() )
view = view.select( resatomid )
mobile_protein_view = mobile_protein_view.select( resatomid )
if view.nSelected() > 0:
mobile_protein_sidechains_group.add( PartialMolecule(new_protein_mol, view) )
except:
pass
try:
backbones = protein_backbones[molnum]
for i in range(0,backbones.nViews()):
view = new_protein_mol.selection()
view = view.selectNone()
for atomid in backbones.viewAt(i).selectedAtoms():
atom = protein_mol.atom(atomid)
resatomid = ResAtomID( atom.residue().number(), atom.name() )
view = view.select( resatomid )
mobile_protein_view = mobile_protein_view.select( resatomid )
if view.nSelected() > 0:
mobile_protein_backbones_group.add( PartialMolecule(new_protein_mol, view) )
except:
pass
if mobile_protein_view.nSelected() > 0:
mobile_proteins_group.add( PartialMolecule(new_protein_mol, mobile_protein_view) )
groups.append(mobile_protein_backbones_group)
groups.append(mobile_protein_sidechains_group)
groups.append(all_group)
# finished added in all of the proteins
for group in groups:
if group.nMolecules() > 0:
print("Adding group %s" % group.name())
system.add(group)
# now add in the forcefields for the system...
print("Creating the forcefields for the QM/MM system...")
# first, group together the molecules grouped above into convenient
# groups for the forcefields
# group holding just the ligand
ligand_mols = ligand_group.molecules()
# group holding all of the mobile atoms
mobile_mols = mobile_solvents_group.molecules()
mobile_mols.add( mobile_solutes_group.molecules() )
mobile_mols.add( protein_intra_group.molecules() )
# group holding all of the mobile atoms in the bound leg, excluding the
# buffer atoms that are fixed, but bonded to mobile atoms
mobile_buffered_mols = mobile_solvents_group.molecules()
mobile_buffered_mols.add( mobile_solutes_group.molecules() )
mobile_buffered_mols.add( mobile_proteins_group.molecules() )
# group holding all of the protein molecules that need intramolecular terms calculated
protein_intra_mols = protein_intra_group.molecules()
# group holding all of the solute molecules that nede intramolecular terms calculated
solute_intra_mols = mobile_solutes_group.molecules()
forcefields = []
###
### INTRA-ENERGY OF THE LIGAND AND CLUSTER
###
# intramolecular energy of the ligand
ligand_intraclj = IntraCLJFF("ligand:intraclj")
ligand_intraclj = setCLJProperties(ligand_intraclj, space)
ligand_intraclj.add(ligand_mols)
ligand_intraff = InternalFF("ligand:intra")
ligand_intraff.add(ligand_mols)
forcefields.append(ligand_intraclj)
forcefields.append(ligand_intraff)
ligand_mm_nrg = ligand_intraclj.components().total() + ligand_intraff.components().total()
###
### FORCEFIELDS INVOLVING THE LIGAND/CLUSTER AND OTHER ATOMS
###
# forcefield holding the energy between the ligand and the mobile atoms in the
# bound leg
ligand_mobile = InterGroupCLJFF("system:ligand-mobile")
ligand_mobile = setCLJProperties(ligand_mobile, space)
ligand_mobile.add(ligand_mols, MGIdx(0))
ligand_mobile.add(mobile_mols, MGIdx(1))
qm_ligand = QMMMFF("system:ligand-QM")
qm_ligand = setQMProperties(qm_ligand, space)
qm_ligand.add(ligand_mols, MGIdx(0))
zero_energy = 0
if not intermolecular_only.val:
if qm_zero_energy.val is None:
# calculate the delta value for the system - this is the difference between
# the MM and QM intramolecular energy of the ligand
t.start()
print("\nComparing the MM and QM energies of the ligand...")
mm_intra = ligand_intraclj.energy().value() + ligand_intraff.energy().value()
print("MM energy = %s kcal mol-1 (took %s ms)" % (mm_intra, t.elapsed()))
t.start()
qm_intra = qm_ligand.energy().value()
print("QM energy = %s kcal mol-1 (took %s ms)" % (qm_intra, t.elapsed()))
print("\nSetting the QM zero energy to %s kcal mol-1" % (qm_intra - mm_intra))
qm_ligand.setZeroEnergy( (qm_intra-mm_intra) * kcal_per_mol )
zero_energy = qm_intra - mm_intra
else:
print("\nManually setting the QM zero energy to %s" % qm_zero_energy.val)
qm_ligand.setZeroEnergy( qm_zero_energy.val )
zero_energy = qm_zero_energy.val
qm_ligand.add(mobile_mols, MGIdx(1))
ligand_mm_nrg += ligand_mobile.components().total()
ligand_qm_nrg = qm_ligand.components().total() + ligand_mobile.components().lj()
if intermolecular_only.val:
# the QM model still uses the MM intramolecular energy of the ligand
ligand_qm_nrg += ligand_intraclj.components().total() + ligand_intraff.components().total()
forcefields.append(ligand_mobile)
forcefields.append(qm_ligand)
if fixed_group.nMolecules() > 0:
# there are fixed molecules
# Whether or not to disable the grid and calculate all energies atomisticly
if disable_grid:
# we need to renumber all of the fixed molecules so that they don't clash
# with the mobile molecules
print("Renumbering fixed molecules...")
fixed_group = renumberMolecules(fixed_group)
# forcefield holding the energy between the ligand and the fixed atoms in the bound leg
if disable_grid:
ligand_fixed = InterGroupCLJFF("system:ligand-fixed")
ligand_fixed = setCLJProperties(ligand_fixed, space)
ligand_fixed = setFakeGridProperties(ligand_fixed, space)
ligand_fixed.add(ligand_mols, MGIdx(0))
ligand_fixed.add(fixed_group, MGIdx(1))
qm_ligand.add(fixed_group, MGIdx(1))
ligand_mm_nrg += ligand_fixed.components().total()
ligand_qm_nrg += ligand_fixed.components().lj()
forcefields.append(ligand_fixed)
else:
ligand_fixed = GridFF("system:ligand-fixed")
ligand_fixed = setCLJProperties(ligand_fixed, space)
ligand_fixed = setGridProperties(ligand_fixed)
ligand_fixed.add(ligand_mols, MGIdx(0))
ligand_fixed.addFixedAtoms( fixed_group )
qm_ligand.addFixedAtoms( fixed_group )
ligand_mm_nrg += ligand_fixed.components().total()
ligand_qm_nrg += ligand_fixed.components().lj()
forcefields.append(ligand_fixed)
###
### FORCEFIELDS NOT INVOLVING THE LIGAND
###
# forcefield holding the intermolecular energy between all molecules
mobile_mobile = InterCLJFF("mobile-mobile")
mobile_mobile = setCLJProperties(mobile_mobile, space)
mobile_mobile.add(mobile_mols)
other_nrg = mobile_mobile.components().total()
forcefields.append(mobile_mobile)
# forcefield holding the energy between the mobile atoms and
# the fixed atoms
if disable_grid.val:
mobile_fixed = InterGroupCLJFF("mobile-fixed")
mobile_fixed = setCLJProperties(mobile_fixed)
mobile_fixed = setFakeGridProperties(mobile_fixed, space)
mobile_fixed.add(mobile_buffered_mols, MGIdx(0))
mobile_fixed.add(fixed_group, MGIdx(1))
other_nrg += mobile_fixed.components().total()
forcefields.append(mobile_fixed)
else:
mobile_fixed = GridFF("mobile-fixed")
mobile_fixed = setCLJProperties(mobile_fixed, space)
mobile_fixed = setGridProperties(mobile_fixed)
# we use mobile_buffered_group as this group misses out atoms that are bonded
# to fixed atoms (thus preventing large energies caused by incorrect non-bonded calculations)
mobile_fixed.add(mobile_buffered_mols, MGIdx(0))
mobile_fixed.addFixedAtoms(fixed_group)
other_nrg += mobile_fixed.components().total()
forcefields.append(mobile_fixed)
# intramolecular energy of the protein
if protein_intra_mols.nMolecules() > 0:
protein_intraclj = IntraCLJFF("protein_intraclj")
protein_intraclj = setCLJProperties(protein_intraclj, space)
protein_intraff = InternalFF("protein_intra")
for molnum in protein_intra_mols.molNums():
protein_mol = protein_intra_mols[molnum].join()
protein_intraclj.add(protein_mol)
protein_intraff.add(protein_mol)
other_nrg += protein_intraclj.components().total()
other_nrg += protein_intraff.components().total()
forcefields.append(protein_intraclj)
forcefields.append(protein_intraff)
# intramolecular energy of any other solutes
if solute_intra_mols.nMolecules() > 0:
solute_intraclj = IntraCLJFF("solute_intraclj")
solute_intraclj = setCLJProperties(solute_intraclj, space)
solute_intraff = InternalFF("solute_intra")
for molnum in solute_intra_mols.molNums():
solute_mol = solute_intra_mols[molnum].join()
solute_intraclj.add(solute_mol)
solute_intraff.add(solute_mol)
other_nrg += solute_intraclj.components().total()
other_nrg += solute_intraff.components().total()
forcefields.append(solute_intraclj)
forcefields.append(solute_intraff)
###
### NOW ADD THE FORCEFIELDS TO THE SYSTEM
###
###
### SETTING THE FORCEFIELD EXPRESSIONS
###
lam = Symbol("lambda")
e_slow = ((1-lam) * ligand_qm_nrg) + (lam * ligand_mm_nrg) + other_nrg
e_fast = ligand_mm_nrg + other_nrg
de_by_dlam = ligand_mm_nrg - ligand_qm_nrg
for forcefield in forcefields:
system.add(forcefield)
system.setConstant(lam, 0.0)
system.setComponent(Symbol("E_{fast}"), e_fast)
system.setComponent(Symbol("E_{slow}"), e_slow)
system.setComponent(Symbol("dE/dlam"), de_by_dlam)
system.setComponent( system.totalComponent(), e_slow )
system.setProperty("space", space)
if space.isPeriodic():
# ensure that all molecules are wrapped into the space with the ligand at the center
print("Adding in a space wrapper constraint %s, %s" % (space, ligand_mol.evaluate().center()))
system.add( SpaceWrapper( ligand_mol.evaluate().center(), all_group ) )
system.applyConstraints()
print("\nHere are the values of all of the initial energy components...")
t.start()
printEnergies(system.energies())
print("(these took %d ms to evaluate)\n" % t.elapsed())
# Create a monitor to monitor the free energy average
system.add( "dG/dlam", MonitorComponent(Symbol("dE/dlam"), AverageAndStddev()) )
if intermolecular_only.val:
print("\n\n## This simulation uses QM to model *only* the intermolecular energy between")
print("## the QM and MM atoms. The intramolecular energy of the QM atoms is still")
print("## modelled using MM.\n")
else:
print("\n\n## This simulation uses QM to model both the intermolecular and intramolecular")
print("## energies of the QM atoms. Because the this, we have to adjust the 'zero' point")
print("## of the QM potential. You need to add the value %s kcal mol-1 back onto the" % zero_energy)
print("## QM->MM free energy calculated using this program.\n")
return system
# Sire performs simulations on simulation System objects.
# A System groups together all of the molecules, forcefields etc.
# into a single unit
system = System()
system.add(cljff)
# Here we create the equation used to calculate the total energy of the
# system. We define a symbol, lambda, which we use here to scale up and
# down the coulomb component of cljff
lam = Symbol("lambda")
total_nrg = cljff.components().lj() + lam * cljff.components().coulomb()
# Here we tell the system to use our equation to calculate the total
# energy, and we set the value of lambda to 0.5
system.setComponent( system.totalComponent(), total_nrg )
system.setConstant( lam, 0.5 )
# Now we create a MoleculeGroup that groups together all of the
# molecules to be moved
mobile_mols = MoleculeGroup("mobile_molecules")
mobile_mols.add(first_water)
mobile_mols.add(second_water)
# We add the molecule group to the system
system.add(mobile_mols)
# We create a periodic boundaries space, and give it to the system
space = PeriodicBox( Vector(5,5,5) )
system.setProperty( "space", space )
# We also add a SpaceWrapper that ensures any moves on mobile_mols
mol = mol.edit().rename("SB2").commit()
mol = protoms.parameterise(mol, ProtoMS.SOLUTE)
perturbations = mol.property("perturbations")
print(perturbations)
print(perturbations.requiredSymbols())
print(perturbations.requiredProperties())
lam = perturbations.symbols().Lambda()
system = System()
solute = MoleculeGroup("solute", mol)
system.add(solute)
system.setConstant(lam, 0.0)
system.add( PerturbationConstraint(solute) )
print(system.constraintsSatisfied())
for i in range(0,101,10):
system.setConstant(lam, 0.01 * i)
PDB().write(system.molecules(), "test_%003d.pdb" % i)
def createSystem():
protomsdir = "%s/Work/ProtoMS" % os.getenv("HOME")
protoms = ProtoMS( "%s/protoms2" % protomsdir )
protoms.addParameterFile( "%s/parameter/amber99.ff" % protomsdir )
protoms.addParameterFile( "%s/parameter/solvents.ff" % protomsdir )
protoms.addParameterFile( "%s/parameter/gaff.ff" % protomsdir )
protoms.addParameterFile( solute_params )
solute = PDB().readMolecule(solute_file)
solute = solute.edit().rename(solute_name).commit()
solute = protoms.parameterise(solute, ProtoMS.SOLUTE)
perturbation = solute.property("perturbations")
lam = Symbol("lambda")
lam_fwd = Symbol("lambda_{fwd}")
lam_bwd = Symbol("lambda_{bwd}")
initial = Perturbation.symbols().initial()
final = Perturbation.symbols().final()
solute = solute.edit().setProperty("perturbations",
perturbation.recreate( (1-lam)*initial + lam*final ) ).commit()
solute_fwd = solute.edit().renumber().setProperty("perturbations",
perturbation.substitute( lam, lam_fwd ) ).commit()
solute_bwd = solute.edit().renumber().setProperty("perturbations",
perturbation.substitute( lam, lam_bwd ) ).commit()
solvent = PDB().read(solvent_file)
tip4p = solvent.moleculeAt(0).molecule()
tip4p = tip4p.edit().rename(solvent_name).commit()
tip4p = protoms.parameterise(tip4p, ProtoMS.SOLVENT)
tip4p_chgs = tip4p.property("charge")
tip4p_ljs = tip4p.property("LJ")
for i in range(0,solvent.nMolecules()):
tip4p = solvent.moleculeAt(i).molecule()
tip4p = tip4p.edit().rename(solvent_name) \
.setProperty("charge", tip4p_chgs) \
.setProperty("LJ", tip4p_ljs) \
.commit()
solvent.update(tip4p)
system = System()
solutes = MoleculeGroup("solutes")
solutes.add(solute)
solutes.add(solute_fwd)
solutes.add(solute_bwd)
solvent = MoleculeGroup("solvent", solvent)
all = MoleculeGroup("all")
all.add(solutes)
all.add(solvent)
system.add(solutes)
system.add(solvent)
system.add(all)
solventff = InterCLJFF("solvent:solvent")
solventff.add(solvent)
solute_intraff = InternalFF("solute_intraff")
solute_intraff.add(solute)
solute_fwd_intraff = InternalFF("solute_fwd_intraff")
solute_fwd_intraff.add(solute_fwd)
solute_bwd_intraff = InternalFF("solute_bwd_intraff")
solute_bwd_intraff.add(solute_bwd)
solute_intraclj = IntraCLJFF("solute_intraclj")
solute_intraclj.add(solute)
solute_fwd_intraclj = IntraCLJFF("solute_fwd_intraclj")
solute_fwd_intraclj.add(solute_fwd)
solute_bwd_intraclj = IntraCLJFF("solute_bwd_intraclj")
solute_bwd_intraclj.add(solute_bwd)
solute_solventff = InterGroupCLJFF("solute:solvent")
solute_solventff.add(solute, MGIdx(0))
solute_solventff.add(solvent, MGIdx(1))
solute_fwd_solventff = InterGroupCLJFF("solute_fwd:solvent")
solute_fwd_solventff.add(solute_fwd, MGIdx(0))
solute_fwd_solventff.add(solvent, MGIdx(1))
solute_bwd_solventff = InterGroupCLJFF("solute_bwd:solvent")
solute_bwd_solventff.add(solute_bwd, MGIdx(0))
solute_bwd_solventff.add(solvent, MGIdx(1))
forcefields = [ solventff, solute_intraff, solute_intraclj, solute_solventff,
solute_fwd_intraff, solute_fwd_intraclj, solute_fwd_solventff,
solute_bwd_intraff, solute_bwd_intraclj, solute_bwd_solventff ]
for forcefield in forcefields:
system.add(forcefield)
xsc_line = open(solvent_file, "r").readlines()[0]
words = xsc_line.split()
#HEADER box -12.5 -12.5 -12.5 12.5 12.5 12.5
space = PeriodicBox( Vector( float(words[2]), float(words[3]), float(words[4]) ),
Vector( float(words[5]), float(words[6]), float(words[7]) ) )
system.setProperty( "space", space )
system.setProperty( "switchingFunction",
HarmonicSwitchingFunction(coulomb_cutoff, coulomb_feather,
lj_cutoff, lj_feather) )
system.setProperty( "combiningRules", VariantProperty(combining_rules) )
e_total = system.totalComponent()
e_fwd = Symbol("E_{fwd}")
e_bwd = Symbol("E_{bwd}")
total_nrg = solventff.components().total() + \
solute_intraclj.components().total() + solute_intraff.components().total() + \
solute_solventff.components().total()
fwd_nrg = solventff.components().total() + \
solute_fwd_intraclj.components().total() + solute_fwd_intraff.components().total() + \
solute_fwd_solventff.components().total()
bwd_nrg = solventff.components().total() + \
solute_bwd_intraclj.components().total() + solute_bwd_intraff.components().total() + \
solute_bwd_solventff.components().total()
system.setComponent( e_total, total_nrg )
system.setComponent( e_fwd, fwd_nrg )
system.setComponent( e_bwd, bwd_nrg )
system.setConstant(lam, 0.0)
system.setConstant(lam_fwd, 0.0)
system.setConstant(lam_bwd, 0.0)
system.add( SpaceWrapper(Vector(0,0,0), all) )
system.add( PerturbationConstraint(solutes) )
system.add( ComponentConstraint( lam_fwd, Min( lam + delta_lambda, 1 ) ) )
system.add( ComponentConstraint( lam_bwd, Max( lam - delta_lambda, 0 ) ) )
de_fwd = Symbol("de_fwd")
de_bwd = Symbol("de_bwd")
system.setComponent( de_fwd, fwd_nrg - total_nrg )
system.setComponent( de_bwd, total_nrg - bwd_nrg )
system.add( "total_energy", MonitorComponent(e_total, Average()) )
system.add( "de_fwd", MonitorComponent(de_fwd, FreeEnergyAverage(temperature)) )
system.add( "de_bwd", MonitorComponent(de_bwd, FreeEnergyAverage(temperature)) )
system.setComponent(lam, 0.0)
print "LAMBDA=0 : Energy = %f kcal mol-1" % system.energy().to(kcal_per_mol)
print " (%f, %f)" % (system.energy(e_fwd).to(kcal_per_mol),
system.energy(e_bwd).to(kcal_per_mol))
system.setComponent(lam, 0.5)
print "LAMBDA=0.5 : Energy = %f kcal mol-1" % system.energy().to(kcal_per_mol)
print " (%f, %f)" % (system.energy(e_fwd).to(kcal_per_mol),
system.energy(e_bwd).to(kcal_per_mol))
system.setComponent(lam, 1.0)
print "LAMBDA=1.0 : Energy = %f kcal mol-1" % system.energy().to(kcal_per_mol)
print " (%f, %f)" % (system.energy(e_fwd).to(kcal_per_mol),
system.energy(e_bwd).to(kcal_per_mol))
return system
# Sire performs simulations on simulation System objects.
# A System groups together all of the molecules, forcefields etc.
# into a single unit
system = System()
system.add(cljff)
# Here we create the equation used to calculate the total energy of the
# system. We define a symbol, lambda, which we use here to scale up and
# down the coulomb component of cljff
lam = Symbol("lambda")
total_nrg = cljff.components().lj() + lam * cljff.components().coulomb()
# Here we tell the system to use our equation to calculate the total
# energy, and we set the value of lambda to 0.5
system.setComponent(system.totalComponent(), total_nrg)
system.setConstant(lam, 0.5)
# Now we create a MoleculeGroup that groups together all of the
# molecules to be moved
mobile_mols = MoleculeGroup("mobile_molecules")
mobile_mols.add(first_water)
mobile_mols.add(second_water)
# We add the molecule group to the system
system.add(mobile_mols)
# We create a periodic boundaries space, and give it to the system
space = PeriodicBox(Vector(5, 5, 5))
system.setProperty("space", space)
# We also add a SpaceWrapper that ensures any moves on mobile_mols
