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# -*- coding:utf-8 -*-
import os
import re
import argparse
import numpy as np
from utils.logger import print_log
from data.converter.blocks_to_data import blocks_to_data
from data.converter.mol2_to_blocks import mol2_to_blocks
from data.converter.pdb_to_list_blocks import pdb_to_list_blocks
from data.mmap_dataset import create_mmap
from data.format import VOCAB, Atom, Block
import copy
import math
def parse():
parser = argparse.ArgumentParser(description='Process PDBBind')
parser.add_argument('--data_dir', type=str, required=True,
help='Directory of scPDB data')
parser.add_argument('--out_dir', type=str, required=True,
help='Output directory')
return parser.parse_args()
def kd_to_dg(kd, temperature=25.0):
"""Conversion of Kd to DG"""
R = 0.0019872043
dg_rt = math.log(kd)
temp_in_k = temperature + 273.15
rt = R * temp_in_k
return dg_rt * rt
def parse_index(fpath):
with open(fpath, 'r') as fin:
lines = fin.readlines()
data = {}
for line in lines:
if line.startswith('#'):
continue
line = re.split(r'\s+', line)
pdb_id, resolution, year, kd = line[:4]
# data[pdb_id] = kd
if (not kd.startswith('Kd')) and (not kd.startswith('Ki')): # IC50 is very different from Kd and Ki, therefore discarded
print_log(f'{pdb_id} not measured by Kd or Ki, dropped.', level='ERROR')
# return None
continue
if '=' not in kd: # some data only provide a threshold, e.g. Kd<1nM, discarded
print_log(f'{pdb_id} Kd only has threshold: {kd}', level='ERROR')
# return None
continue
kd = kd.split('=')[-1].strip()
aff, unit = float(kd[:-2]), kd[-2:]
if unit == 'mM':
aff *= 1e-3
elif unit == 'nM':
aff *= 1e-9
elif unit == 'uM':
aff *= 1e-6
elif unit == 'pM':
aff *= 1e-12
elif unit == 'fM':
aff *= 1e-15
else:
# return None # unrecognizable unit
continue
# affinity data
data[pdb_id] = {
'Kd': aff,
'dG': kd_to_dg(aff, 25.0), # regard as measured under the standard condition
'neglog_aff': -math.log(aff, 10) # pK = -log_10 (Kd)
}
return data
def blocks_to_coords(blocks: List[Block]):
max_n_unit = 0
coords, masks = [], []
for block in blocks:
coords.append([unit.get_coord() for unit in block.units])
max_n_unit = max(max_n_unit, len(coords[-1]))
masks.append([1 for _ in coords[-1]])
for i in range(len(coords)):
num_pad = max_n_unit - len(coords[i])
coords[i] = coords[i] + [[0, 0, 0] for _ in range(num_pad)]
masks[i] = masks[i] + [0 for _ in range(num_pad)]
return np.array(coords), np.array(masks).astype('bool') # [N, M, 3], [N, M], M == max_n_unit, in mask 0 is for padding
def dist_matrix_from_coords(coords1, masks1, coords2, masks2):
dist = np.linalg.norm(coords1[:, None] - coords2[None, :], axis=-1) # [N1, N2, M]
dist = dist + np.logical_not(masks1[:, None] * masks2[None, :]) * 1e6 # [N1, N2, M]
dist = np.min(dist, axis=-1) # [N1, N2]
return dist
def dist_matrix_from_residues(residue_list1, residue_list2):
coords, mask = blocks_to_coords(residue_list1 + residue_list2)
midpoint = len(residue_list1)
coords1, masks1 = coords[:midpoint], mask[:midpoint]
coords2, masks2 = coords[midpoint:], mask[midpoint:]
return dist_matrix_from_coords(coords1, masks1, coords2, masks2)
def blocks_interface(blocks1, blocks2, dist_th):
blocks_coord, blocks_mask = blocks_to_coords(blocks1 + blocks2)
blocks1_coord, blocks1_mask = blocks_coord[:len(blocks1)], blocks_mask[:len(blocks1)]
blocks2_coord, blocks2_mask = blocks_coord[len(blocks1):], blocks_mask[len(blocks1):]
dist = dist_matrix_from_coords(blocks1_coord, blocks1_mask, blocks2_coord, blocks2_mask)
on_interface = dist < dist_th
indexes1 = np.nonzero(on_interface.sum(axis=1) > 0)[0]
indexes2 = np.nonzero(on_interface.sum(axis=0) > 0)[0]
blocks1 = [blocks1[i] for i in indexes1]
blocks2 = [blocks2[i] for i in indexes2]
return blocks1, blocks2
def break_blocks_into_atoms(blocks):
block_list = []
for block in blocks:
for atom in block.units:
atom_new = copy.deepcopy(atom)
atom_new.pos_code = VOCAB.atom_pos_sm
block_list.append(
Block(symbol=atom_new.element.lower(), units = [atom_new])
)
return block_list
def process_iterator_PP(data_dir, index_file, dist_th = 6.0):
indexes = parse_index(index_file)
for pdb_id in indexes:
list_blocks, chains = pdb_to_list_blocks(os.path.join(data_dir, f'{pdb_id}.ent.pdb'), return_chain_ids=True)
if len(list_blocks) != 2:
continue
rec_residues, lig_residues = list_blocks # [Q] I can't visit FASTA. Swapping the order of the two chains may not actually change the logic of the following codes?
rec_inter, lig_inter = blocks_interface(rec_residues, lig_residues, dist_th)
list_blocks = [rec_inter, lig_inter]
data = blocks_to_data(*list_blocks)
for key in data:
if isinstance(data[key], np.ndarray):
data[key] = data[key].tolist()
Kd, dG, neglog_aff = indexes[pdb_id]['Kd'], indexes[pdb_id]['dG'], indexes[pdb_id]['neglog_aff']
yield pdb_id, data, [len(data['B']), Kd, dG, neglog_aff]
def process_iterator_PL(data_dir, index_file, dist_th = 6.0):
indexes = parse_index(index_file)
for pdb_id in indexes:
if not os.path.exists(os.path.join(data_dir, pdb_id)):
continue
prot_fname = os.path.join(data_dir, pdb_id, f'{pdb_id}_protein.pdb')
sm_fname = os.path.join(data_dir, pdb_id, f'{pdb_id}_ligand.mol2')
list_blocks1 = pdb_to_list_blocks(prot_fname)
blocks2 = mol2_to_blocks(sm_fname)
blocks1 = []
for b in list_blocks1:
blocks1.extend(b)
# construct pockets
blocks1, _ = blocks_interface(blocks1, blocks2, dist_th)
list_blocks = [blocks1, blocks2]
data = blocks_to_data(*list_blocks)
for key in data:
if isinstance(data[key], np.ndarray):
data[key] = data[key].tolist()
Kd, dG, neglog_aff = indexes[pdb_id]['Kd'], indexes[pdb_id]['dG'], indexes[pdb_id]['neglog_aff']
yield pdb_id, data, [len(data['B']), Kd, dG, neglog_aff]
def process_iterator_NL(data_dir, index_file, dist_th = 6.0):
indexes = parse_index(index_file)
for pdb_id in indexes:
if not os.path.exists(os.path.join(data_dir, pdb_id)):
continue
list_blocks, chains = pdb_to_list_blocks(os.path.join(data_dir, f'{pdb_id}.ent.pdb'), return_chain_ids=True)
bases = ['DA', 'DG', 'DC', 'DT', 'R-A', 'R-G', 'R-C', 'R-U']
rec_blocks = []
lig_blocks = []
for chain in list_blocks:
split_point = None
for i in range(len(chain)):
residue = chain[len(chain) - i - 1]
if residue.symbol in bases:
split_point = len(chain) - i
break
rec_blocks.extend(chain[:split_point])
lig_blocks.extend(break_blocks_into_atoms(chain[split_point:]))
# construct pockets
rec_interface, _ = blocks_interface(rec_blocks, lig_blocks, dist_th)
list_blocks = [rec_interface, lig_blocks]
data = blocks_to_data(*list_blocks)
for key in data:
if isinstance(data[key], np.ndarray):
data[key] = data[key].tolist()
Kd, dG, neglog_aff = indexes[pdb_id]['Kd'], indexes[pdb_id]['dG'], indexes[pdb_id]['neglog_aff']
yield pdb_id, data, [len(data['B']), Kd, dG, neglog_aff]
def main(args):
print_log(f'Processing PP')
PP_index_file = os.path.join(args.data_dir, 'PP', 'index', 'INDEX_general_PP.2020')
PP_index = parse_index(PP_index_file)
create_mmap(
process_iterator_PP(os.path.join(args.data_dir, 'PP')),
PP_index_file,
os.path.join(args.out_dir, 'PP-aff'), len(PP_index)
)
print_log(f'Processing PL refined set')
PL_refine_index_file = os.path.join(args.data_dir, 'refined-set', 'index', 'INDEX_refined_set.2020')
PL_refine_index = parse_index(PL_refine_index_file)
create_mmap(
process_iterator_PL(
os.path.join(args.data_dir, 'refined-set'),
PL_refine_index_file,
), os.path.join(args.out_dir, 'refined-set-aff'), len(PL_refine_index)
)
print_log(f'Processing PL others')
PL_other_index_file = os.path.join(args.data_dir, 'v2020-other-PL', 'index', 'INDEX_general_PL.2020')
PL_other_index = parse_index(PL_other_index_file)
create_mmap(
process_iterator_PL(
os.path.join(args.data_dir, 'v2020-other-PL'),
PL_other_index_file,
), os.path.join(args.out_dir, 'v2020-other-PL-aff'), len(PL_other_index) - len(PL_refine_index)
)
print_log(f'Processing PN')
PN_index_file = os.path.join(args.data_dir, 'PN', 'index', 'INDEX_general_PN.2020')
PN_index = parse_index(PN_index_file)
create_mmap(
process_iterator_PP(os.path.join(args.data_dir, 'PN')),
PN_index_file,
os.path.join(args.out_dir, 'PN-aff'), len(PN_index)
)
print_log(f'Processing NL')
NL_index_file = os.path.join(args.data_dir, 'NL', 'index', 'INDEX_general_NL.2020')
NL_index = parse_index(PP_index_file)
create_mmap(
process_iterator_NL(os.path.join(args.data_dir, 'NL')),
NL_index_file,
os.path.join(args.out_dir, 'NL-aff'), len(NL_index)
)
print_log('Finished!')
if __name__ == '__main__':
main(parse())
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