########################################################################################################################
__doc__ = \
"""
This is a variant of Victor for MPro that uses data from PostEra
"""
########################################################################################################################
from typing import List, Optional
from warnings import warn
import pandas as pd
import pyrosetta
from rdkit import Chem
from ..demo import MPro as data # noqa this is basically a package, but actually a class
from ..victor import Victor
from .dataframe import fetch_postera, read_postera
[docs]
class MProVictor(Victor):
constraint_function_type = 'FLAT_HARMONIC'
[docs]
@classmethod
def from_hit_codes(cls, hit_codes: List[str], **options):
hits = [data.get_mol(xnumber) for xnumber in hit_codes]
return cls(hits=hits, **options)
[docs]
@staticmethod
def pose_fx(pose: pyrosetta.Pose):
"""
Histidine protonated on epsilon — HIE.
"""
pdb2pose = pose.pdb_info().pdb2pose
r = pdb2pose(res=41, chain='A')
MutateResidue = pyrosetta.rosetta.protocols.simple_moves.MutateResidue
MutateResidue(target=r, new_res='HIS').apply(pose)
[docs]
@staticmethod
def poised_pose_fx(pose: pyrosetta.Pose):
"""
Histidine protonated on delta (HID) and cysteine in thiolate.
"""
# Americans spell poise as poise not poize.
pdb2pose = pose.pdb_info().pdb2pose
r = pdb2pose(res=41, chain='A')
MutateResidue = pyrosetta.rosetta.protocols.simple_moves.MutateResidue
MutateResidue(target=r, new_res='HIS_D').apply(pose)
r = pdb2pose(res=145, chain='A')
MutateResidue(target=r, new_res='CYZ').apply(pose)
[docs]
def __init__(self, category:Optional[str]=None, **options):
# this category flag is solely for Mpro?
# it stems from the Moonshot file.
self.category = category
if category == 'noncolavent':
fx = self.__class__.poised_pose_fx
else:
fx = self.__class__.pose_fx
# --------------------
defaults = dict(
pdb_block=data.get_template(),
ligand_resn='LIG',
ligand_resi='1B',
covalent_resn='CYS',
covalent_resi='145A',
extra_protein_constraint='AtomPair SG 145A NE2 41A HARMONIC 3.5 0.2\n',
pose_fx=fx # from the above.
)
super().__init__(**{**defaults, **options})
def _determine_extras(self, smiles):
defaults = dict()
if self.category not in (None, 'noncovalent') and '_' in self.category:
cname, rxd = self.category.split('_')
if rxd == 'noncovalent':
wd = [wd for wd in self.warhead_definitions if wd['name'] == cname][0]
mol = Chem.MolFromSmiles(smiles)
nc = Chem.MolFromSmiles(wd['noncovalent'])
atomnames = dict(zip(mol.GetSubstructMatch(nc), wd['noncovalent_atomnames']))
extra_constraint = 'AtomPair SG 145A CX 1B HARMONIC 3.2 0.5\n'
extra_constraint += wd['constraint']
defaults = dict(atomnames=atomnames,
extra_ligand_constraint=extra_constraint)
return defaults
#self.combine(**options) unchanged.
[docs]
def place(self, *args, **options):
defaults = self._determine_extras(options['smiles'] if 'smiles' in options else args[0])
# singledispatchmethod does not like named args
kwargs = {**defaults, **options}
return super().place(*args, **kwargs)
# ======= postera csv file ops =====================================================================================
[docs]
@classmethod
def fetch_postera(cls):
__doc__ = fetch_postera.__doc__
warn('method moved to mpro_data (as function)', category=DeprecationWarning)
return fetch_postera()
[docs]
@classmethod
def analyse_postera(cls):
raise NotImplementedError('Incomplete functionality')
[docs]
@classmethod
def from_postera_row(cls, row: pd.Series, results:Optional=None):
if row.fragments == 'x0072' or str(row.fragments) == 'nan':
# these are not hit inspired.
cls.journal.error(f'No valid parent hits for {row.CID}.')
return None
elif results and row.CID in results:
cls.journal.info(f'{row.CID} has already been done.')
return None
elif row.covalent_warhead in (False, 'False', 'false'):
# parse
return cls.from_hit_codes(hit_codes=row.fragments.split(','),
category='noncolavent')\
.place(long_name=row.CID,
smiles=row.SMILES)
elif row.category not in ('Acrylamide', 'Chloroacetamide', 'Vinylsulfonamide', 'Nitrile'):
cls.journal.info(f'What is {row["CID"]}? Treating like a non-covalent.')
return cls.from_hit_codes(hit_codes=row.fragments.split(','),
category='noncolavent')\
.place(long_name=row.CID,
smiles=row.SMILES)
else:
return cls.from_hit_codes(hit_codes=row.fragments.split(','),
category=row.category)\
.place(long_name=row.CID,
smiles=row.SMILES)
#### Update the dataset with constraints specific for MPro
for cname, con in [('chloroacetamide', 'AtomPair H 145A OY 1B HARMONIC 2.1 0.2\n'),
('nitrile', 'AtomPair H 145A NX 1B HARMONIC 2.1 0.2\n'),
('acrylamide', 'AtomPair H 143A OZ 1B HARMONIC 2.1 0.2\n'),
('vinylsulfonamide', 'AtomPair H 143A OZ1 1B HARMONIC 2.1 0.2\n'),
('bromoalkyne', 'AtomPair H 145A CY 1B HARMONIC 2.1 0.2\n'),
]:
MProVictor.add_constraint_to_warhead(name=cname, constraint=con)