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