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Commit af2e3c2f authored by peastman's avatar peastman
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Implemented matching of residues to single-residue patches

parent c1d35c3e
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Showing with 191 additions and 33 deletions
wrappers/python/simtk/openmm/app/forcefield.py
View file @ af2e3c2f
...@@ -206,8 +206,8 @@ class ForceField(object): ...@@ -206,8 +206,8 @@ class ForceField(object):
template.addExternalBond(int(bond.attrib['from'])) template.addExternalBond(int(bond.attrib['from']))
for patch in residue.findall('AllowPatch'): for patch in residue.findall('AllowPatch'):
patchName = patch.attrib['name'] patchName = patch.attrib['name']
if ':' in name: if ':' in patchName:
colonIndex = name.find(':') colonIndex = patchName.find(':')
self.registerTemplatePatch(resName, patchName[:colonIndex], int(patchName[colonIndex+1:])-1) self.registerTemplatePatch(resName, patchName[:colonIndex], int(patchName[colonIndex+1:])-1)
else: else:
self.registerTemplatePatch(resName, patchName, 0) self.registerTemplatePatch(resName, patchName, 0)
...@@ -487,6 +487,16 @@ class ForceField(object): ...@@ -487,6 +487,16 @@ class ForceField(object):
else: else:
self.constraints[key] = distance self.constraints[key] = distance
system.addConstraint(atom1, atom2, distance) system.addConstraint(atom1, atom2, distance)
def recordMatchedAtomParameters(self, residue, template, matches):
"""Record parameters for atoms based on having matched a residue to a template."""
matchAtoms = dict(zip(matches, residue.atoms()))
for atom, match in zip(residue.atoms(), matches):
self.atomType[atom] = template.atoms[match].type
self.atomParameters[atom] = template.atoms[match].parameters
for site in template.virtualSites:
if match == site.index:
self.virtualSites[atom] = (site, [matchAtoms[i].index for i in site.atoms], matchAtoms[site.excludeWith].index)
class _TemplateData(object): class _TemplateData(object):
"""Inner class used to encapsulate data about a residue template definition.""" """Inner class used to encapsulate data about a residue template definition."""
...@@ -611,15 +621,17 @@ class ForceField(object): ...@@ -611,15 +621,17 @@ class ForceField(object):
for atom in template.atoms: for atom in template.atoms:
if not any(deleted.name == atom.name and deleted.residue == index for deleted in self.deletedAtoms): if not any(deleted.name == atom.name and deleted.residue == index for deleted in self.deletedAtoms):
newTemplate.atoms.append(deepcopy(atom)) newTemplate.atoms.append(ForceField._TemplateAtomData(atom.name, atom.type, atom.element, atom.parameters))
for atom in self.addedAtoms[index]: for atom in self.addedAtoms[index]:
newTemplate.atoms.append(deepcopy(atom)) if any(a.name == atom.name for a in newTemplate.atoms):
raise ValueError("Patch '%s' adds an atom with the same name as an existing atom: %s" % (self.name, atom.name))
newTemplate.atoms.append(ForceField._TemplateAtomData(atom.name, atom.type, atom.element, atom.parameters))
oldAtomIndex = dict([(atom.name, i) for i, atom in enumerate(template.atoms)]) oldAtomIndex = dict([(atom.name, i) for i, atom in enumerate(template.atoms)])
newAtomIndex = dict([(atom.name, i) for i, atom in enumerate(newTemplate.atoms)]) newAtomIndex = dict([(atom.name, i) for i, atom in enumerate(newTemplate.atoms)])
for atom in self.changedAtoms[index]: for atom in self.changedAtoms[index]:
if atom.name not in newAtomIndex: if atom.name not in newAtomIndex:
raise ValueError("Patch '%s' modifies nonexistent atom '%s' in template '%s'" % (self.name, atom.name, template.name)) raise ValueError("Patch '%s' modifies nonexistent atom '%s' in template '%s'" % (self.name, atom.name, template.name))
newTemplate.atoms[newAtomIndex[atom.name]] = deepcopy(atom) newTemplate.atoms[newAtomIndex[atom.name]] = ForceField._TemplateAtomData(atom.name, atom.type, atom.element, atom.parameters)
# Copy over the virtual sites, translating the atom indices. # Copy over the virtual sites, translating the atom indices.
...@@ -643,7 +655,7 @@ class ForceField(object): ...@@ -643,7 +655,7 @@ class ForceField(object):
deletedExternalBonds = [atom.name for atom in self.deletedExternalBonds if atom.residue == index] deletedExternalBonds = [atom.name for atom in self.deletedExternalBonds if atom.residue == index]
for atom in template.externalBonds: for atom in template.externalBonds:
if template.atoms[atom].name not in deletedExternalBonds: if template.atoms[atom].name not in deletedExternalBonds:
newTemplate.addExternalBond(atomMap[atom]) newTemplate.addExternalBond(indexMap[atom])
for atom1, atom2 in self.addedBonds: for atom1, atom2 in self.addedBonds:
if atom1.residue == index and atom2.residue == index: if atom1.residue == index and atom2.residue == index:
newTemplate.addBondByName(atom1.name, atom2.name) newTemplate.addBondByName(atom1.name, atom2.name)
...@@ -745,7 +757,7 @@ class ForceField(object): ...@@ -745,7 +757,7 @@ class ForceField(object):
raise ValueError('%s: No parameters defined for atom type %s' % (self.forceName, t)) raise ValueError('%s: No parameters defined for atom type %s' % (self.forceName, t))
def _getResidueTemplateMatches(self, res, bondedToAtom): def _getResidueTemplateMatches(self, res, bondedToAtom, templateSignatures=None):
"""Return the residue template matches, or None if none are found. """Return the residue template matches, or None if none are found.
Parameters Parameters
...@@ -766,10 +778,12 @@ class ForceField(object): ...@@ -766,10 +778,12 @@ class ForceField(object):
""" """
template = None template = None
matches = None matches = None
if templateSignatures is None:
templateSignatures = self._templateSignatures
signature = _createResidueSignature([atom.element for atom in res.atoms()]) signature = _createResidueSignature([atom.element for atom in res.atoms()])
if signature in self._templateSignatures: if signature in templateSignatures:
allMatches = [] allMatches = []
for t in self._templateSignatures[signature]: for t in templateSignatures[signature]:
match = _matchResidue(res, t, bondedToAtom) match = _matchResidue(res, t, bondedToAtom)
if match is not None: if match is not None:
allMatches.append((t, match)) allMatches.append((t, match))
...@@ -975,8 +989,8 @@ class ForceField(object): ...@@ -975,8 +989,8 @@ class ForceField(object):
data.atomBonds[bond.atom2].append(i) data.atomBonds[bond.atom2].append(i)
# Find the template matching each residue and assign atom types. # Find the template matching each residue and assign atom types.
# If no templates are found, attempt to use residue template generators to create new templates (and potentially atom types/parameters).
unmatchedResidues = []
for chain in topology.chains(): for chain in topology.chains():
for res in chain.residues(): for res in chain.residues():
if res in residueTemplates: if res in residueTemplates:
...@@ -989,30 +1003,37 @@ class ForceField(object): ...@@ -989,30 +1003,37 @@ class ForceField(object):
# Attempt to match one of the existing templates. # Attempt to match one of the existing templates.
[template, matches] = self._getResidueTemplateMatches(res, bondedToAtom) [template, matches] = self._getResidueTemplateMatches(res, bondedToAtom)
if matches is None: if matches is None:
# No existing templates match. Try any registered residue template generators. unmatchedResidues.append(res)
for generator in self._templateGenerators: else:
if generator(self, res): data.recordMatchedAtomParameters(res, template, matches)
# This generator has registered a new residue template that should match.
[template, matches] = self._getResidueTemplateMatches(res, bondedToAtom) # Try to apply patches to find matches for any unmatched residues.
if matches is None:
# Something went wrong because the generated template does not match the residue signature. if len(unmatchedResidues) > 0:
raise Exception('The residue handler %s indicated it had correctly parameterized residue %s, but the generated template did not match the residue signature.' % (generator.__class__.__name__, str(res))) unmatchedResidues = _applyPatchesToMatchResidues(self, data, unmatchedResidues, bondedToAtom)
else:
# We successfully generated a residue template. Break out of the for loop. # If we still haven't found a match for a residue, attempt to use residue template generators to create
break # new templates (and potentially atom types/parameters).
# Raise an exception if we have found no templates that match.
if matches is None:
raise ValueError('No template found for residue %d (%s). %s' % (res.index+1, res.name, _findMatchErrors(self, res)))
# Store parameters for the matched residue template. for res in unmatchedResidues:
matchAtoms = dict(zip(matches, res.atoms())) # A template might have been generated on an earlier iteration of this loop.
for atom, match in zip(res.atoms(), matches): [template, matches] = self._getResidueTemplateMatches(res, bondedToAtom)
data.atomType[atom] = template.atoms[match].type if matches is None:
data.atomParameters[atom] = template.atoms[match].parameters # Try all generators.
for site in template.virtualSites: for generator in self._templateGenerators:
if match == site.index: if generator(self, res):
data.virtualSites[atom] = (site, [matchAtoms[i].index for i in site.atoms], matchAtoms[site.excludeWith].index) # This generator has registered a new residue template that should match.
[template, matches] = self._getResidueTemplateMatches(res, bondedToAtom)
if matches is None:
# Something went wrong because the generated template does not match the residue signature.
raise Exception('The residue handler %s indicated it had correctly parameterized residue %s, but the generated template did not match the residue signature.' % (generator.__class__.__name__, str(res)))
else:
# We successfully generated a residue template. Break out of the for loop.
break
if matches is None:
raise ValueError('No template found for residue %d (%s). %s' % (res.index+1, res.name, _findMatchErrors(self, res)))
else:
data.recordMatchedAtomParameters(res, template, matches)
# Create the System and add atoms # Create the System and add atoms
...@@ -1289,6 +1310,58 @@ def _findAtomMatches(atoms, template, bondedTo, externalBonds, matches, hasMatch ...@@ -1289,6 +1310,58 @@ def _findAtomMatches(atoms, template, bondedTo, externalBonds, matches, hasMatch
return False return False
def _applyPatchesToMatchResidues(forcefield, data, residues, bondedToAtom):
"""Try to apply patches to find matches for residues."""
# Start by creating all templates than can be created by applying a combination of one-residue patches
# to a single template. The number of these is usually not too large, and they often cover a large fraction
# of residues.
patchedTemplateSignatures = {}
patchedTemplates = {}
for name, template in forcefield._templates.items():
if name in forcefield._templatePatches:
patches = [forcefield._patches[patchName] for patchName, patchResidueIndex in forcefield._templatePatches[name] if forcefield._patches[patchName].numResidues == 1]
if len(patches) > 0:
newTemplates = []
patchedTemplates[name] = newTemplates
_generatePatchedSingleResidueTemplates(template, patches, 0, newTemplates)
for patchedTemplate in newTemplates:
signature = _createResidueSignature([atom.element for atom in patchedTemplate.atoms])
if signature in patchedTemplateSignatures:
patchedTemplateSignatures[signature].append(patchedTemplate)
else:
patchedTemplateSignatures[signature] = [patchedTemplate]
# Now see if any of those templates matches any of the residues.
unmatchedResidues = []
for res in residues:
[template, matches] = forcefield._getResidueTemplateMatches(res, bondedToAtom, patchedTemplateSignatures)
if matches is None:
unmatchedResidues.append(res)
else:
data.recordMatchedAtomParameters(res, template, matches)
return unmatchedResidues
def _generatePatchedSingleResidueTemplates(template, patches, index, newTemplates):
"""Apply all possible combinations of a set of single-residue patches to a template."""
try:
patchedTemplate = patches[index].createPatchedTemplates([template])[0]
newTemplates.append(patchedTemplate)
except:
# This probably means the patch is inconsistent with another one that has already been applied,
# so just ignore it.
patchedTemplate = None
# Call this function recursively to generate combinations of patches.
if index+1 < len(patches):
_generatePatchedSingleResidueTemplates(template, patches, index+1, newTemplates)
if patchedTemplate is not None:
_generatePatchedSingleResidueTemplates(patchedTemplate, patches, index+1, newTemplates)
def _findMatchErrors(forcefield, res): def _findMatchErrors(forcefield, res):
"""Try to guess why a residue failed to match any template and return an error message.""" """Try to guess why a residue failed to match any template and return an error message."""
residueCounts = _countResidueAtoms([atom.element for atom in res.atoms()]) residueCounts = _countResidueAtoms([atom.element for atom in res.atoms()])
......
wrappers/python/tests/TestPatches.py
View file @ af2e3c2f
...@@ -176,5 +176,90 @@ class TestForceField(unittest.TestCase): ...@@ -176,5 +176,90 @@ class TestForceField(unittest.TestCase):
self.assertEqual(indexMap['B'], v.atoms[0]) self.assertEqual(indexMap['B'], v.atoms[0])
self.assertEqual(indexMap['C'], v.atoms[1]) self.assertEqual(indexMap['C'], v.atoms[1])
def testAlaAlaAla(self):
"""Test constructing a System that involves two patches."""
xml = """
<ForceField>
<AtomTypes>
<Type name="N" class="N" element="N" mass="14.00672"/>
<Type name="H" class="H" element="H" mass="1.007947"/>
<Type name="CT" class="CT" element="C" mass="12.01078"/>
<Type name="H1" class="H1" element="H" mass="1.007947"/>
<Type name="HC" class="HC" element="H" mass="1.007947"/>
<Type name="C" class="C" element="C" mass="12.01078"/>
<Type name="O" class="O" element="O" mass="15.99943"/>
<Type name="O2" class="O2" element="O" mass="15.99943"/>
<Type name="N3" class="N3" element="N" mass="14.00672"/>
</AtomTypes>
<Residues>
<Residue name="ALA">
<Atom name="N" type="N"/>
<Atom name="H" type="H"/>
<Atom name="CA" type="CT"/>
<Atom name="HA" type="H1"/>
<Atom name="CB" type="CT"/>
<Atom name="HB1" type="HC"/>
<Atom name="HB2" type="HC"/>
<Atom name="HB3" type="HC"/>
<Atom name="C" type="C"/>
<Atom name="O" type="O"/>
<Bond from="0" to="1"/>
<Bond from="0" to="2"/>
<Bond from="2" to="3"/>
<Bond from="2" to="4"/>
<Bond from="2" to="8"/>
<Bond from="4" to="5"/>
<Bond from="4" to="6"/>
<Bond from="4" to="7"/>
<Bond from="8" to="9"/>
<ExternalBond from="0"/>
<ExternalBond from="8"/>
<AllowPatch name="CTER"/>
<AllowPatch name="NTER"/>
</Residue>
</Residues>
<Patches>
<Patch name="CTER">
<AddAtom name="OXT" type="O2"/>
<ChangeAtom name="O" type="O2"/>
<AddBond atomName1="C" atomName2="OXT"/>
<RemoveExternalBond atomName="C"/>
</Patch>
<Patch name="NTER">
<RemoveAtom name="H"/>
<AddAtom name="H1" type="H"/>
<AddAtom name="H2" type="H"/>
<AddAtom name="H3" type="H"/>
<ChangeAtom name="N" type="N3"/>
<RemoveBond atomName1="N" atomName2="H"/>
<AddBond atomName1="N" atomName2="H1"/>
<AddBond atomName1="N" atomName2="H2"/>
<AddBond atomName1="N" atomName2="H3"/>
<RemoveExternalBond atomName="N"/>
</Patch>
</Patches>
<NonbondedForce coulomb14scale="0.833333" lj14scale="0.5">
<Atom type="N" charge="-0.4157" sigma="0.324999852378" epsilon="0.71128"/>
<Atom type="H" charge="0.2719" sigma="0.106907846177" epsilon="0.0656888"/>
<Atom type="CT" charge="0.0337" sigma="0.339966950842" epsilon="0.4577296"/>
<Atom type="H1" charge="0.0823" sigma="0.247135304412" epsilon="0.0656888"/>
<Atom type="HC" charge="0.0603" sigma="0.264953278775" epsilon="0.0656888"/>
<Atom type="C" charge="0.5973" sigma="0.339966950842" epsilon="0.359824"/>
<Atom type="O" charge="-0.5679" sigma="0.295992190115" epsilon="0.87864"/>
<Atom type="O2" charge="-0.8055" sigma="0.295992190115" epsilon="0.87864"/>
<Atom type="N3" charge="0.1414" sigma="0.324999852378" epsilon="0.71128"/>
</NonbondedForce>
</ForceField>"""
ff = ForceField(StringIO(xml))
pdb = PDBFile(os.path.join('systems', 'ala_ala_ala.pdb'))
system = ff.createSystem(pdb.topology)
nb = system.getForce(0)
expectedCharges = [0.1414, 0.2719, 0.2719, 0.2719, 0.0337, 0.0823, 0.0337, 0.0603, 0.0603, 0.0603, 0.5973, -0.5679,
-0.4157, 0.2719, 0.0337, 0.0823, 0.0337, 0.0603, 0.0603, 0.0603, 0.5973, -0.5679,
0.5973, -0.8055, -0.8055, -0.4157, 0.2719, 0.0337, 0.0823, 0.0337, 0.0603, 0.0603, 0.0603]
for i in range(system.getNumParticles()):
self.assertEqual(expectedCharges[i], nb.getParticleParameters(i)[0].value_in_unit(elementary_charge))
if __name__ == '__main__': if __name__ == '__main__':
unittest.main() unittest.main()
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