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calc-accessibility.py
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calc-accessibility.py
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import argparse
import sys
import logging
import os
from freesasa import Structure
import pkg_resources
default_bases = ["DA", "DC", "DG", "DT", "A", "C", "G", "U"]
modified_bases = ["DJ"]
standard_aa = ['ALA', 'ARG', 'ASN', 'ASP', 'CYS', 'GLN', 'GLU', 'GLY', 'HIS', 'ILE', 'LEU', 'LYS', 'MET', 'PHE', 'PRO',
'SER', 'THR', 'TRP', 'TYR', 'VAL']
modified_aa = ['ACE', 'ALY', 'ASH', 'CFE', 'CHX', 'CSP', 'CTN', 'CYC', 'CYF', 'CYM', 'DDZ', 'DUM', 'GLH', 'HLY', 'HYP',
'M3L', 'MLY', 'MLZ', 'MSE', 'NEP', 'PNS', 'PTR', 'SEP', 'TOP', 'TYP', 'TYS'] # , 'THP'='TOP'?
valid_aa = standard_aa + modified_aa
valid_bases = default_bases + modified_bases
valid_ions = ["LI", "F", "NA", "MG", "AL", "CL", "K", "CA", "V", "CR", "MN", "FE", "NI", "CO", "CU", "ZN",
"BR", "KR", "SR", "MO", "AG", "CD", "I", "CS", "HO", "YB", "OS", "IR", "PT", "AU", "HG", "PB"]
# Taken from NACCESS
rel_asa = {
'total':
{
'ALA': 107.95,
'CYS': 134.28,
'ASP': 140.39,
'GLU': 172.25,
'PHE': 199.48,
'GLY': 80.10,
'HIS': 182.88,
'ILE': 175.12,
'LYS': 200.81,
'LEU': 178.63,
'MET': 194.15,
'ASN': 143.94,
'PRO': 136.13,
'GLN': 178.50,
'ARG': 238.76,
'SER': 116.50,
'THR': 139.27,
'VAL': 151.44,
'TRP': 249.36,
'TYR': 212.76,
'ASH': 140.39,
'DDZ': 107.95,
'GLH': 172.25,
'CYM': 134.28,
'CSP': 134.28,
'CYF': 134.28,
'CYC': 134.28,
'CFE': 134.28,
'NEP': 182.88,
'ALY': 200.81,
'MLZ': 200.81,
'MLY': 200.81,
'M3L': 200.81,
'HYP': 136.13,
'SEP': 116.50,
'TOP': 139.27,
'TYP': 212.76,
'PTR': 212.76,
'TYS': 212.76,
'PNS': 116.50,
},
'bb':
{
'ALA': 38.54,
'CYS': 37.53,
'ASP': 37.70,
'GLU': 37.51,
'PHE': 35.37,
'GLY': 47.77,
'HIS': 35.80,
'ILE': 37.16,
'LYS': 37.51,
'LEU': 37.51,
'MET': 37.51,
'ASN': 37.70,
'PRO': 16.23,
'GLN': 37.51,
'ARG': 37.51,
'SER': 38.40,
'THR': 37.57,
'VAL': 37.16,
'TRP': 38.10,
'TYR': 35.38,
'ASH': 37.70,
'DDZ': 38.54,
'GLH': 37.51,
'CYM': 37.53,
'CYC': 37.53,
'CSP': 37.53,
'CYF': 37.53,
'CFE': 37.53,
'NEP': 35.80,
'ALY': 37.51,
'MLZ': 37.51,
'MLY': 37.51,
'M3L': 37.51,
'HYP': 16.23,
'SEP': 38.40,
'TOP': 37.57,
'TYP': 35.38,
'PTR': 35.38,
'TYS': 35.38,
'PNS': 38.40,
},
'sc':
{
'ALA': 69.41,
'CYS': 96.75,
'ASP': 102.69,
'GLU': 134.74,
'PHE': 164.11,
'GLY': 32.33,
'HIS': 147.08,
'ILE': 137.96,
'LYS': 163.30,
'LEU': 141.12,
'MET': 156.64,
'ASN': 106.24,
'PRO': 119.90,
'GLN': 140.99,
'ARG': 201.25,
'SER': 78.11,
'THR': 101.70,
'VAL': 114.28,
'TRP': 211.26,
'TYR': 177.38,
'ASH': 102.69,
'DDZ': 69.41,
'GLH': 134.74,
'CYM': 96.75,
'CYC': 96.75,
'CSP': 96.75,
'CYF': 96.75,
'CFE': 96.75,
'NEP': 147.08,
'ALY': 163.30,
'MLZ': 163.30,
'MLY': 163.30,
'M3L': 163.30,
'HYP': 119.90,
'SEP': 78.11,
'TOP': 101.70,
'TYP': 177.38,
'PTR': 177.38,
'TYS': 177.38,
'PNS': 78.11,
}
}
def get_accessibility(pdb_f):
"""Calls `FreeSASA <https://freesasa.github.io/>`_ using its Python API and returns per-residue accessibility
values."""
naccess_unsupported_aa = ['HEC', 'TIP', 'ACE', 'THP', 'HEB', 'CTN']
logging.info("Calculate accessibility...")
try:
from freesasa import Classifier, structureFromBioPDB, calc
except ImportError as err:
print('[!] The binding affinity prediction tools require the \'freesasa\' Python API', file=sys.stderr)
raise ImportError(err)
asa_data, rsa_data, rel_main_chain, rel_side_chain = {}, {}, {}, {}
_rsa = rel_asa['total']
_rsa_bb = rel_asa['bb']
_rsa_sc = rel_asa['sc']
# Workaround to get relative accessibility values for Nucleic Acids (will always be accessible)
for na in valid_bases:
_rsa[na] = 1
_rsa_bb[na] = 1
_rsa_sc[na] = 1
config_path = '/'.join(os.path.realpath(__file__).split('/')[:-1]) + '/naccess.config'
classifier = Classifier(config_path)
pkg_resources.cleanup_resources()
struct = Structure(pdb_f, classifier, options={})
struct.setRadiiWithClassifier(classifier)
result = calc(struct)
# iterate over all atoms to get SASA and residue name
for idx in range(struct.nAtoms()):
atname = struct.atomName(idx).strip()
resname = struct.residueName(idx).strip()
resid = int(struct.residueNumber(idx))
chain = struct.chainLabel(idx)
at_uid = (chain, resname, resid, atname)
res_uid = (chain, resname, resid)
asa = result.atomArea(idx)
asa_data[at_uid] = asa
# add asa to residue
rsa_data[res_uid] = rsa_data.get(res_uid, 0) + asa
# If residue name is unknown, this is probably an ion, set a relative accessibility of -1
if resname not in _rsa and (resname not in valid_aa + valid_bases or resname[:2] in valid_ions
or resname in naccess_unsupported_aa):
logging.warning(f"UPDATED RSA for {resname}")
_rsa[resname] = -1
_rsa_bb[resname] = -1
_rsa_sc[resname] = -1
# 3 cases: Regular amino-acid, regular nucleic acid, ion
if (resname not in valid_bases and atname in ('C', 'N', 'O')) or \
(resname in valid_bases and atname in ('P', 'C1', 'C9')):
rel_main_chain[res_uid] = rel_main_chain.get(res_uid, 0) + asa
elif resname not in valid_aa + valid_bases and resname[:2] in valid_ions:
rel_main_chain[res_uid] = rel_main_chain.get(res_uid, 0) + asa
rel_side_chain[res_uid] = rel_side_chain.get(res_uid, 0) + asa
else:
rel_side_chain[res_uid] = rel_side_chain.get(res_uid, 0) + asa
# convert total asa ro relative asa
rsa_data.update((res_uid, asa / _rsa[res_uid[1]]) for res_uid, asa in rsa_data.items())
rel_main_chain.update((res_uid, asa / _rsa_bb[res_uid[1]] * 100) for res_uid, asa in rel_main_chain.items())
rel_side_chain.update((res_uid, asa / _rsa_sc[res_uid[1]] * 100) for res_uid, asa in rel_side_chain.items())
# We format to fit the pipeline
resid_access = {}
for res_uid, access in rel_main_chain.items():
chain = res_uid[0]
# resname = res_uid[1]
resnum = res_uid[2]
if chain not in resid_access:
resid_access[chain] = {}
resid_access[chain][resnum] = {'side_chain_rel': rel_side_chain.get(res_uid, 0), 'main_chain_rel': access}
for chain in resid_access:
logging.info(f"Chain: {chain} - {len(resid_access[chain])} residues")
return resid_access
def apply_cutoff(access_data, cutoff):
"""Apply a cutoff to the sidechain relative accessibility and display on stdout"""
logging.info(f'Applying cutoff to side_chain_rel - {cutoff}')
for chain in access_data:
result_list = []
for res in access_data[chain]:
sidechain_relative_accessibility = access_data[chain][res]['side_chain_rel']
if sidechain_relative_accessibility >= cutoff * 100:
result_list.append(res)
result_list = list(set(result_list))
result_list.sort()
result_str = ','.join(map(str, result_list))
logging.info(f'Chain {chain} - {result_str}')
if __name__ == "__main__":
parser = argparse.ArgumentParser()
levels = ('DEBUG', 'INFO', 'WARNING', 'ERROR', 'CRITICAL')
parser.add_argument('--log-level', default='INFO', choices=levels)
parser.add_argument('--cutoff', default=0.4, type=float, help='Relative cutoff for sidechain accessibility')
parser.add_argument("pdb_input", help='PDB structure')
args = parser.parse_args()
logging.basicConfig(level=args.log_level,
format='%(asctime)s L%(lineno)d %(levelname)s - %(message)s',
datefmt='%d/%m/%Y %H:%M:%S')
access_dic = get_accessibility(args.pdb_input)
apply_cutoff(access_dic, args.cutoff)