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https://github.com/baker-laboratory/RoseTTAFold-All-Atom.git
synced 2024-09-15 22:08:31 +00:00
309 lines
12 KiB
Python
309 lines
12 KiB
Python
import torch
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from openbabel import openbabel
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from typing import Optional
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from dataclasses import dataclass
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from tempfile import NamedTemporaryFile
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from rf2aa.chemical import ChemicalData as ChemData
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from rf2aa.data.parsers import parse_mol
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from rf2aa.data.small_molecule import compute_features_from_obmol
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from rf2aa.util import get_bond_feats
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@dataclass
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class MoleculeToMoleculeBond:
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chain_index_first: int
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absolute_atom_index_first: int
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chain_index_second: int
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absolute_atom_index_second: int
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new_chirality_atom_first: Optional[str]
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new_chirality_atom_second: Optional[str]
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@dataclass
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class AtomizedResidue:
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chain: str
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chain_index_in_combined_chain: int
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absolute_N_index_in_chain: int
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absolute_C_index_in_chain: int
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original_chain: str
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index_in_original_chain: int
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def load_covalent_molecules(protein_inputs, config, model_runner):
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if config.covale_inputs is None:
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return None
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if config.sm_inputs is None:
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raise ValueError("If you provide covale_inputs, you must also provide small molecule inputs")
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covalent_bonds = eval(config.covale_inputs)
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sm_inputs = delete_leaving_atoms(config.sm_inputs)
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residues_to_atomize, combined_molecules, extra_bonds = find_residues_to_atomize(protein_inputs, sm_inputs, covalent_bonds, model_runner)
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chainid_to_input = {}
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for chain, combined_molecule in combined_molecules.items():
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extra_bonds_for_chain = extra_bonds[chain]
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msa, bond_feats, xyz, Ls = get_combined_atoms_bonds(combined_molecule)
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residues_to_atomize = update_absolute_indices_after_combination(residues_to_atomize, chain, Ls)
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mol = make_obmol_from_atoms_bonds(msa, bond_feats, xyz, Ls, extra_bonds_for_chain)
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xyz = recompute_xyz_after_chirality(mol)
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input = compute_features_from_obmol(mol, msa, xyz, model_runner)
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chainid_to_input[chain] = input
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return chainid_to_input, residues_to_atomize
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def find_residues_to_atomize(protein_inputs, sm_inputs, covalent_bonds, model_runner):
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residues_to_atomize = [] # hold on to delete wayward inputs
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combined_molecules = {} # combined multiple molecules that are bonded
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extra_bonds = {}
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for bond in covalent_bonds:
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prot_chid, prot_res_idx, atom_to_bond = bond[0]
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sm_chid, sm_atom_num = bond[1]
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chirality_first_atom, chirality_second_atom = bond[2]
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if chirality_first_atom.strip() == "null":
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chirality_first_atom = None
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if chirality_second_atom.strip() == "null":
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chirality_second_atom = None
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sm_atom_num = int(sm_atom_num) - 1 # 0 index
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try:
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assert sm_chid in sm_inputs, f"must provide a small molecule chain {sm_chid} for covalent bond: {bond}"
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except:
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print(f"Skipping bond: {bond} since no sm chain {sm_chid} was provided")
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continue
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assert sm_inputs[sm_chid].input_type == "sdf", "only sdf inputs can be covalently linked to proteins"
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try:
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protein_input = protein_inputs[prot_chid]
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except Exception as e:
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raise ValueError(f"first atom in covale_input must be present in\
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a protein chain. Given chain: {prot_chid} was not in \
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given protein chains: {list(protein_inputs.keys())}")
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residue = (prot_chid, prot_res_idx, atom_to_bond)
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file, atom_index = convert_residue_to_molecule(protein_inputs, residue, model_runner)
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if sm_chid not in combined_molecules:
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combined_molecules[sm_chid] = [sm_inputs[sm_chid].input]
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combined_molecules[sm_chid].insert(0, file) # this is a bug, revert
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absolute_chain_index_first = combined_molecules[sm_chid].index(sm_inputs[sm_chid].input)
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absolute_chain_index_second = combined_molecules[sm_chid].index(file)
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if sm_chid not in extra_bonds:
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extra_bonds[sm_chid] = []
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extra_bonds[sm_chid].append(MoleculeToMoleculeBond(
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absolute_chain_index_first,
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sm_atom_num,
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absolute_chain_index_second,
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atom_index,
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new_chirality_atom_first=chirality_first_atom,
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new_chirality_atom_second=chirality_second_atom
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))
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residues_to_atomize.append(AtomizedResidue(
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sm_chid,
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absolute_chain_index_second,
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0,
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2,
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prot_chid,
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int(prot_res_idx) -1
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))
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return residues_to_atomize, combined_molecules, extra_bonds
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def convert_residue_to_molecule(protein_inputs, residue, model_runner):
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"""convert residue into sdf and record index for covalent bond"""
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prot_chid, prot_res_idx, atom_to_bond = residue
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protein_input = protein_inputs[prot_chid]
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prot_res_abs_idx = int(prot_res_idx) -1
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residue_identity_num = protein_input.query_sequence()[prot_res_abs_idx]
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residue_identity = ChemData().num2aa[residue_identity_num]
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molecule_info = model_runner.molecule_db[residue_identity]
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sdf = molecule_info["sdf"]
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temp_file = create_and_populate_temp_file(sdf)
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is_heavy = [i for i, a in enumerate(molecule_info["atom_id"]) if a[0] != "H"]
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is_leaving = [a for i,a in enumerate(molecule_info["leaving"]) if i in is_heavy]
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sdf_string_no_leaving_atoms = delete_leaving_atoms_single_chain(temp_file, is_leaving )
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temp_file = create_and_populate_temp_file(sdf_string_no_leaving_atoms)
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atom_names = molecule_info["atom_id"]
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atom_index = atom_names.index(atom_to_bond.strip())
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return temp_file, atom_index
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def get_combined_atoms_bonds(combined_molecule):
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atom_list = []
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bond_feats_list = []
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xyzs = []
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Ls = []
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for molecule in combined_molecule:
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obmol, msa, ins, xyz, mask = parse_mol(
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molecule,
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filetype="sdf",
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string=False,
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generate_conformer=True,
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find_automorphs=False
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)
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bond_feats = get_bond_feats(obmol)
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atom_list.append(msa)
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bond_feats_list.append(bond_feats)
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xyzs.append(xyz)
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Ls.append(msa.shape[0])
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atoms = torch.cat(atom_list)
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L_total = sum(Ls)
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bond_feats = torch.zeros((L_total, L_total)).long()
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offset = 0
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for bf in bond_feats_list:
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L = bf.shape[0]
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bond_feats[offset:offset+L, offset:offset+L] = bf
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offset += L
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xyz = torch.cat(xyzs, dim=1)[0]
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return atoms, bond_feats, xyz, Ls
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def make_obmol_from_atoms_bonds(msa, bond_feats, xyz, Ls, extra_bonds):
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mol = openbabel.OBMol()
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for i,k in enumerate(msa):
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element = ChemData().num2aa[k]
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atomnum = ChemData().atomtype2atomnum[element]
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a = mol.NewAtom()
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a.SetAtomicNum(atomnum)
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a.SetVector(float(xyz[i,0]), float(xyz[i,1]), float(xyz[i,2]))
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first_index, second_index = bond_feats.nonzero(as_tuple=True)
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for i, j in zip(first_index, second_index):
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order = bond_feats[i,j]
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bond = make_openbabel_bond(mol, i.item(), j.item(), order.item())
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mol.AddBond(bond)
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for bond in extra_bonds:
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absolute_index_first = get_absolute_index_from_relative_indices(
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bond.chain_index_first,
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bond.absolute_atom_index_first,
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Ls
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)
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absolute_index_second = get_absolute_index_from_relative_indices(
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bond.chain_index_second,
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bond.absolute_atom_index_second,
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Ls
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)
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order = 1 #all covale bonds are single bonds
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openbabel_bond = make_openbabel_bond(mol, absolute_index_first, absolute_index_second, order)
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mol.AddBond(openbabel_bond)
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set_chirality(mol, absolute_index_first, bond.new_chirality_atom_first)
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set_chirality(mol, absolute_index_second, bond.new_chirality_atom_second)
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return mol
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def make_openbabel_bond(mol, i, j, order):
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obb = openbabel.OBBond()
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obb.SetBegin(mol.GetAtom(i+1))
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obb.SetEnd(mol.GetAtom(j+1))
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if order == 4:
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obb.SetBondOrder(2)
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obb.SetAromatic()
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else:
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obb.SetBondOrder(order)
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return obb
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def set_chirality(mol, absolute_atom_index, new_chirality):
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stereo = openbabel.OBStereoFacade(mol)
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if stereo.HasTetrahedralStereo(absolute_atom_index+1):
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tetstereo = stereo.GetTetrahedralStereo(mol.GetAtom(absolute_atom_index+1).GetId())
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if tetstereo is None:
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return
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assert new_chirality is not None, "you have introduced a new stereocenter, \
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so you must specify its chirality either as CW, or CCW"
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config = tetstereo.GetConfig()
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config.winding = chirality_options[new_chirality]
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tetstereo.SetConfig(config)
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print("Updating chirality...")
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else:
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assert new_chirality is None, "you have specified a chirality without creating a new chiral center"
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chirality_options = {
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"CW": openbabel.OBStereo.Clockwise,
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"CCW": openbabel.OBStereo.AntiClockwise,
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}
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def recompute_xyz_after_chirality(obmol):
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builder = openbabel.OBBuilder()
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builder.Build(obmol)
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ff = openbabel.OBForceField.FindForceField("mmff94")
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did_setup = ff.Setup(obmol)
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if did_setup:
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ff.FastRotorSearch()
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ff.GetCoordinates(obmol)
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else:
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raise ValueError(f"Failed to generate 3D coordinates for molecule {filename}.")
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atom_coords = torch.tensor([[obmol.GetAtom(i).x(),obmol.GetAtom(i).y(), obmol.GetAtom(i).z()]
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for i in range(1, obmol.NumAtoms()+1)]).unsqueeze(0) # (1, natoms, 3)
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return atom_coords
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def delete_leaving_atoms(sm_inputs):
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updated_sm_inputs = {}
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for chain in sm_inputs:
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if "is_leaving" not in sm_inputs[chain]:
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continue
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is_leaving = eval(sm_inputs[chain]["is_leaving"])
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sdf_string = delete_leaving_atoms_single_chain(sm_inputs[chain]["input"], is_leaving)
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updated_sm_inputs[chain] = {
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"input": create_and_populate_temp_file(sdf_string),
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"input_type": "sdf"
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}
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sm_inputs.update(updated_sm_inputs)
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return sm_inputs
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def delete_leaving_atoms_single_chain(filename, is_leaving):
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obmol, msa, ins, xyz, mask = parse_mol(
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filename,
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filetype="sdf",
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string=False,
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generate_conformer=True
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)
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assert len(is_leaving) == obmol.NumAtoms()
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leaving_indices = torch.tensor(is_leaving).nonzero()
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for idx in leaving_indices:
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obmol.DeleteAtom(obmol.GetAtom(idx.item()+1))
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obConversion = openbabel.OBConversion()
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obConversion.SetInAndOutFormats("sdf", "sdf")
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sdf_string = obConversion.WriteString(obmol)
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return sdf_string
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def get_absolute_index_from_relative_indices(chain_index, absolute_index_in_chain, Ls):
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offset = sum(Ls[:chain_index])
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return offset + absolute_index_in_chain
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def update_absolute_indices_after_combination(residues_to_atomize, chain, Ls):
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updated_residues_to_atomize = []
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for residue in residues_to_atomize:
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if residue.chain == chain:
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absolute_index_N = get_absolute_index_from_relative_indices(
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residue.chain_index_in_combined_chain,
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residue.absolute_N_index_in_chain,
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Ls)
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absolute_index_C = get_absolute_index_from_relative_indices(
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residue.chain_index_in_combined_chain,
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residue.absolute_C_index_in_chain,
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Ls)
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updated_residue = AtomizedResidue(
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residue.chain,
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None,
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absolute_index_N,
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absolute_index_C,
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residue.original_chain,
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residue.index_in_original_chain
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)
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updated_residues_to_atomize.append(updated_residue)
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else:
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updated_residues_to_atomize.append(residue)
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return updated_residues_to_atomize
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def create_and_populate_temp_file(data):
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# Create a temporary file
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with NamedTemporaryFile(mode='w+', delete=False) as temp_file:
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# Write the string to the temporary file
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temp_file.write(data)
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# Get the filename
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temp_file_name = temp_file.name
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return temp_file_name
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