def rebuild_c_terminal(complex: oechem.OEGraphMol) -> oechem.OEGraphMol:
# Delete and rebuild C-terminal residue because Spruce causes issues with this
# See: 6m2n 6lze
pred = oechem.OEIsCTerminalAtom()
for atom in complex.GetAtoms():
if pred(atom):
for nbor in atom.GetAtoms():
if oechem.OEGetPDBAtomIndex(nbor) == oechem.OEPDBAtomName_O:
complex.DeleteAtom(nbor)
return complex
def mutate_structure(target_structure: oechem.OEGraphMol,
template_sequence: str) -> oechem.OEGraphMol:
"""
Mutate a protein structure according to an amino acid sequence.
Parameters
----------
target_structure: oechem.OEGraphMol
An OpenEye molecule holding a protein structure to mutate.
template_sequence: str
A template one letter amino acid sequence, which defines the sequence the target structure should be mutated
to. Protein residues not matching a template sequence will be either mutated or deleted.
Returns
-------
mutated_structure: oechem.OEGraphMol
An OpenEye molecule holding the mutated protein structure.
"""
from Bio import pairwise2
# the hierarchy view is more stable if reinitialized after each change
# https://docs.eyesopen.com/toolkits/python/oechemtk/biopolymers.html#a-hierarchy-view
finished = False
while not finished:
altered = False
# align template and target sequences
target_sequence = get_sequence(target_structure)
template_sequence_aligned, target_sequence_aligned = pairwise2.align.globalxs(
template_sequence, target_sequence, -10, 0)[0][:2]
logging.debug(f"Template sequence:\n{template_sequence}")
logging.debug(f"Target sequence:\n{target_sequence}")
hierview = oechem.OEHierView(target_structure)
structure_residues = hierview.GetResidues()
# adjust target structure to match template sequence
for template_sequence_residue, target_sequence_residue in zip(
template_sequence_aligned, target_sequence_aligned):
if template_sequence_residue == "-":
# delete any non protein residue from target structure
structure_residue = structure_residues.next()
if target_sequence_residue != "X":
# delete
for atom in structure_residue.GetAtoms():
target_structure.DeleteAtom(atom)
# break loop and reinitialize
altered = True
break
else:
# compare amino acids
if target_sequence_residue != "-":
structure_residue = structure_residues.next()
if target_sequence_residue not in [
"X", template_sequence_residue
]:
# mutate
structure_residue = structure_residue.GetOEResidue()
three_letter_code = oechem.OEGetResidueName(
oechem.OEGetResidueIndexFromCode(
template_sequence_residue))
oespruce.OEMutateResidue(target_structure,
structure_residue,
three_letter_code)
# break loop and reinitialize
altered = True
break
# leave while loop if no changes were introduced
if not altered:
finished = True
# OEMutateResidue doesn't build sidechains and doesn't add hydrogens automatically
oespruce.OEBuildSidechains(target_structure)
oechem.OEPlaceHydrogens(target_structure)
# update residue information
oechem.OEPerceiveResidues(target_structure, oechem.OEPreserveResInfo_All)
return target_structure
