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pdbfixer
Commit cde53ba9 by Peter Eastman
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Can add missing heavy atoms while preserving all existing atoms

parent 41c9f421
Showing with 141 additions and 89 deletions
pdbfixer.py
......@@ -72,6 +72,105 @@ def overlayPoints(points1, points2):
(u, s, v) = lin.svd(R)
return (-1*center2, np.dot(u, v).transpose(), center1)
def addMissingAtoms(pdb, templates, missingAtoms, heavyAtomsOnly, omitUnknownMolecules):
"""Create a new Topology in which missing atoms have been added."""
newTopology = app.Topology()
newPositions = []*unit.nanometer
newAtoms = []
existingAtomMap = {}
addedAtomMap = {}
addedOXT = []
for chain in pdb.topology.chains():
if omitUnknownMolecules and not any(residue.name in templates for residue in chain.residues()):
continue
newChain = newTopology.addChain()
chainResidues = list(chain.residues())
for residue in chain.residues():
newResidue = newTopology.addResidue(residue.name, newChain)
# Add the existing heavy atoms.
for atom in residue.atoms():
if not heavyAtomsOnly or (atom.element is not None and atom.element != hydrogen):
newAtom = newTopology.addAtom(atom.name, atom.element, newResidue)
newAtoms.append(newAtom)
existingAtomMap[atom] = newAtom
newPositions.append(pdb.positions[atom.index])
if residue in missingAtoms:
# Find corresponding atoms in the residue and the template.
template = templates[residue.name]
atomPositions = dict((atom.name, pdb.positions[atom.index]) for atom in residue.atoms())
points1 = []
points2 = []
for atom in template.topology.atoms():
if atom.name in atomPositions:
points1.append(atomPositions[atom.name].value_in_unit(unit.nanometer))
points2.append(template.positions[atom.index].value_in_unit(unit.nanometer))
# Compute the optimal transform to overlay them.
(translate2, rotate, translate1) = overlayPoints(points1, points2)
# Add the missing atoms.
addedAtomMap[residue] = {}
for atom in missingAtoms[residue]:
newAtom = newTopology.addAtom(atom.name, atom.element, newResidue)
newAtoms.append(newAtom)
addedAtomMap[residue][atom] = newAtom
templatePosition = template.positions[atom.index].value_in_unit(unit.nanometer)
newPositions.append((mm.Vec3(*np.dot(rotate, templatePosition+translate2))+translate1)*unit.nanometer)
# If a terminal OXT is missing, add it.
if residue == chainResidues[-1] and residue.name in templates:
atomPositions = dict((atom.name, pdb.positions[atom.index].value_in_unit(unit.nanometer)) for atom in residue.atoms())
if 'OXT' not in atomPositions and all(name in atomPositions for name in ['C', 'O', 'CA']):
newAtom = newTopology.addAtom('OXT', oxygen, newResidue)
newAtoms.append(newAtom)
addedOXT.append(newAtom)
d_ca_o = atomPositions['O']-atomPositions['CA']
d_ca_c = atomPositions['C']-atomPositions['CA']
d_ca_c /= unit.sqrt(unit.dot(d_ca_c, d_ca_c))
v = d_ca_o - d_ca_c*unit.dot(d_ca_c, d_ca_o)
newPositions.append((atomPositions['O']+2*v)*unit.nanometer)
# Add bonds from the original Topology.
for atom1, atom2 in pdb.topology.bonds():
if atom1 in existingAtomMap and atom2 in existingAtomMap:
newTopology.addBond(existingAtomMap[atom1], existingAtomMap[atom2])
# Add bonds that connect to new atoms.
for residue in missingAtoms:
template = templates[residue.name]
atomsByName = dict((atom.name, atom) for atom in residue.atoms())
addedAtoms = addedAtomMap[residue]
for atom1, atom2 in template.topology.bonds():
if atom1 in addedAtoms or atom2 in addedAtoms:
if atom1 in addedAtoms:
bondAtom1 = addedAtoms[atom1]
else:
bondAtom1 = existingAtomMap[atomsByName[atom1.name]]
if atom2 in addedAtoms:
bondAtom2 = addedAtoms[atom2]
else:
bondAtom2 = existingAtomMap[atomsByName[atom2.name]]
newTopology.addBond(bondAtom1, bondAtom2)
for atom1 in addedOXT:
atom2 = [atom for atom in atom1.residue.atoms() if atom.name == 'C'][0]
newTopology.addBond(atom1, atom2)
# Return the results.
return (newTopology, newPositions, newAtoms, existingAtomMap)
# Load the PDB file.
pdb = app.PDBFile(sys.argv[1])
......@@ -98,93 +197,47 @@ for residue in pdb.topology.residues():
if len(missing) > 0:
missingAtoms[residue] = missing
# Create the new Topology.
newTopology = app.Topology()
newPositions = []*unit.nanometer
existingAtomMap = {}
addedAtomMap = {}
addedOXT = []
for chain in pdb.topology.chains():
newChain = newTopology.addChain()
chainResidues = list(chain.residues())
for residue in chain.residues():
newResidue = newTopology.addResidue(residue.name, newChain)
# Add the existing heavy atoms.
for atom in residue.atoms():
if atom.element is not None and atom.element != hydrogen:
newAtom = newTopology.addAtom(atom.name, atom.element, newResidue)
existingAtomMap[atom] = newAtom
newPositions.append(pdb.positions[atom.index])
if residue in missingAtoms:
# Find corresponding atoms in the residue and the template.
template = templates[residue.name]
atomPositions = dict((atom.name, pdb.positions[atom.index]) for atom in residue.atoms())
points1 = []
points2 = []
for atom in template.topology.atoms():
if atom.name in atomPositions:
points1.append(atomPositions[atom.name].value_in_unit(unit.nanometer))
points2.append(template.positions[atom.index].value_in_unit(unit.nanometer))
# Compute the optimal transform to overlay them.
(translate2, rotate, translate1) = overlayPoints(points1, points2)
# Add the missing atoms.
addedAtomMap[residue] = {}
for atom in missingAtoms[residue]:
newAtom = newTopology.addAtom(atom.name, atom.element, newResidue)
addedAtomMap[residue][atom] = newAtom
templatePosition = template.positions[atom.index].value_in_unit(unit.nanometer)
newPositions.append((mm.Vec3(*np.dot(rotate, templatePosition+translate2))+translate1)*unit.nanometer)
# If a terminal OXT is missing, add it.
if residue == chainResidues[-1] and residue.name in templates:
atomPositions = dict((atom.name, pdb.positions[atom.index].value_in_unit(unit.nanometer)) for atom in residue.atoms())
if 'OXT' not in atomPositions and all(name in atomPositions for name in ['C', 'O', 'CA']):
newAtom = newTopology.addAtom('OXT', oxygen, newResidue)
addedOXT.append(newAtom)
d_ca_o = atomPositions['O']-atomPositions['CA']
d_ca_c = atomPositions['C']-atomPositions['CA']
d_ca_c /= unit.sqrt(unit.dot(d_ca_c, d_ca_c))
v = d_ca_o - d_ca_c*unit.dot(d_ca_c, d_ca_o)
newPositions.append((atomPositions['O']+2*v)*unit.nanometer)
# Add bonds from the original Topology.
for atom1, atom2 in pdb.topology.bonds():
if atom1 in existingAtomMap and atom2 in existingAtomMap:
newTopology.addBond(existingAtomMap[atom1], existingAtomMap[atom2])
# Add bonds that connect to new atoms.
for residue in missingAtoms:
template = templates[residue.name]
atomsByName = dict((atom.name, atom) for atom in residue.atoms())
addedAtoms = addedAtomMap[residue]
for atom1, atom2 in template.topology.bonds():
if atom1 in addedAtoms or atom2 in addedAtoms:
if atom1 in addedAtoms:
bondAtom1 = addedAtoms[atom1]
else:
bondAtom1 = existingAtomMap[atomsByName[atom1.name]]
if atom2 in addedAtoms:
bondAtom2 = addedAtoms[atom2]
else:
bondAtom2 = existingAtomMap[atomsByName[atom2.name]]
newTopology.addBond(bondAtom1, bondAtom2)
for atom1 in addedOXT:
atom2 = [atom for atom in atom1.residue.atoms() if atom.name == 'C'][0]
newTopology.addBond(atom1, atom2)
app.PDBFile.writeFile(newTopology, newPositions, open('output.pdb', 'w'))
# Create a Topology that 1) adds missing atoms, 2) removes all hydrogens, and 3) removes unknown molecules.
(newTopology, newPositions, newAtoms, existingAtomMap) = addMissingAtoms(pdb, templates, missingAtoms, True, True)
# Create a System for energy minimizing it.
forcefield = app.ForceField('soft.xml')
forcefield.createSystem(newTopology)
\ No newline at end of file
system = forcefield.createSystem(newTopology)
# Set any previously existing atoms to be massless, they so won't move.
for atom in existingAtomMap.itervalues():
system.setParticleMass(atom.index, 0.0)
# If any heavy atoms were omitted, add them back to avoid steric clashes.
nonbonded = [f for f in system.getForces() if isinstance(f, mm.CustomNonbondedForce)][0]
for atom in pdb.topology.atoms():
if atom.element is not None and atom.element != hydrogen and atom not in existingAtomMap:
system.addParticle(0.0)
nonbonded.addParticle([])
newPositions.append(pdb.positions[atom.index])
# For efficiency, only compute interactions that involve a new atom.
nonbonded.addInteractionGroup([atom.index for atom in newTopology.atoms() if atom in newAtoms], range(system.getNumParticles()))
# Do an energy minimization.
integrator = mm.LangevinIntegrator(300*unit.kelvin, 10/unit.picosecond, 5*unit.femtosecond)
context = mm.Context(system, integrator)
context.setPositions(newPositions)
mm.LocalEnergyMinimizer.minimize(context)
state = context.getState(getPositions=True)
# Now create a new Topology, including all atoms from the original one and adding the missing atoms.
(newTopology2, newPositions2, newAtoms2, existingAtomMap2) = addMissingAtoms(pdb, templates, missingAtoms, False, False)
# Copy over the minimized positions for the new atoms.
for a1, a2 in zip(newAtoms, newAtoms2):
newPositions2[a2.index] = state.getPositions()[a1.index]
app.PDBFile.writeFile(newTopology2, newPositions2, open('output.pdb', 'w'))
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