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FragmentsMerging.py
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FragmentsMerging.py
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import argparse
import sys, os, glob
from utils.io import read_sdf, write_sdf
from Alignment import align
def make_dirs(prefix, target_r_groups):
if prefix != "":
prefix += "_"
os.system(f"mkdir -p {prefix}refs")
os.system(f"mkdir -p {prefix}merged")
os.system(f"mkdir -p {prefix}pdb_params")
os.system(f"mkdir -p {prefix}replaced_params_ref")
os.system(f"mkdir -p {prefix}complexes")
os.system(f"mkdir -p {prefix}minimizations")
for i in range(target_r_groups):
os.system(f"mkdir -p {prefix}target_R{i+2}")
os.system(f"mkdir -p {prefix}alns_R{i+2}")
os.system(f"mkdir -p {prefix}replaced_params_R{i+2}")
return f"{prefix}refs", [f"{prefix}target_R{i+2}" for i in range(target_r_groups)],\
[f"{prefix}alns_R{i+2}" for i in range(target_r_groups)],\
f"{prefix}merged", f"{prefix}pdb_params", f"{prefix}replaced_params_ref",\
[f"{prefix}replaced_params_R{i+2}" for i in range(target_r_groups)],\
f"{prefix}complexes", f"{prefix}minimizations"
def args():
parser = argparse.ArgumentParser()
parser.add_argument("-out_prefix", default="")
parser.add_argument("-ref_pdb", required=True)
parser.add_argument("-ref_params", required=True)
parser.add_argument("-target_pdb", nargs="+", required=True)
parser.add_argument("-target_params", nargs="+", required=True)
parser.add_argument("-substructure", required=True)
parser.add_argument("-klifs_seq", nargs="+", required=True)
args = parser.parse_args()
return args
def alignment(ref, targ, substructure, output):
ref_pose = read_sdf(ref, add_hs=False)[0]
target_pose = read_sdf(targ, add_hs=False)[0]
substructure_pose = read_sdf(substructure, add_hs=False, remove_hs=True)[0]
target_pose_aln, rmsd = align(target_pose, ref_pose, substructure=substructure_pose)
write_sdf(target_pose_aln, output, status="w")
return output, rmsd
def merging(ref, targets, core, output):
p = os.path.realpath(__file__)
p = p[0:p.rfind("/")+1]
targets = " ".join(targets)
cmd = f"python {p}/Merging.py -ref_pose {ref} -target_pose {targets} -substructure {core} -output {output}"
os.system(cmd)
def cmd_am1bcc_charge(input_sdf, output_mol):
if os.getenv("OECHARGE"):
os.system(f"python $OECHARGE -method am1bcc -in {input_sdf} -out {output_mol}")
elif os.getenv("OBABEL"):
os.system("obabel -isdf {input_sdf} -omol2 > {output_mol}")
else:
raise("Please install OEChem or OpenBabel")
def cmd_params(input_mol2, output_prefix):
os.system(f"python $MOL2GENPARAMS -s {input_mol2} --prefix={output_prefix}")
def cmd_replace_params(ref_pdb, ref_params, input_pdb, input_params, output_params):
p = os.path.realpath(__file__)
p = p[0:p.rfind("/")+1]
os.system(f"python {p}/Params.py -ref_pdb {ref_pdb} -ref_params {ref_params} -target_pdb {input_pdb} -target_params {input_params} -out {output_params}")
def minimization(ligand, protein, params, hinge):
complexx = f"complexes/{ligand.split('/')[-1].split('.')[0]}.pdb"
cmd = f"cat {protein} {ligand} > {complexx}"
os.system(cmd)
mini_complexx = f"minimizations/mini_{complexx.split('/')[-1]}"
mini_log = f"minimizations/mini_{complexx.split('/')[-1].split('.')[0]}.log"
cmd = f"python Screening.py -pdb {complexx} -params {params} -output {mini_complexx} -residues {hinge} > {mini_log}"
os.system(cmd)
def extract_lig_prot(input_pdb, output_ligand_pdb, output_protein_pdb):
with open(input_pdb, "r") as f:
f = f.read().split("\n")
atoms = []
hetatms = []
for line in f:
if line == "":
continue
if line.startswith("ATOM"):
atoms.append(line)
elif line.startswith("HETATM"):
hetatms.append(line)
with open(output_ligand_pdb, "w") as f:
f.write("\n".join(hetatms))
f.close()
with open(output_protein_pdb, "w") as f:
f.write("\n".join(atoms))
f.write("\nTER\n")
f.close()
def cmd_convert_pdb_to_sdf(input_pdb, params, output_sdf):
p = os.path.realpath(__file__)
p = p[0:p.rfind("/")+1]
os.system(f"python {p}/ConvertPDBtoSDF.py -inp {input_pdb} -params {params} -out {output_sdf}")
def cmd_concat(protein, input_pdb, output_pdb):
os.system(f"cat {protein} {input_pdb} > {output_pdb}")
def cmd_minimization(input_pdb, input_params, input_klifs, output_pdb, output_log):
p = os.path.realpath(__file__)
p = p[0:p.rfind("/")+1]
input_klifs = " ".join(input_klifs)
os.system(f"python {p}/Screening.py -pdb {input_pdb} -params {input_params} -residues {input_klifs} -output {output_pdb} > {output_log}")
if __name__ == "__main__":
args = args()
dirs = make_dirs(args.out_prefix, len(args.target_pdb))
refs_dir = dirs[0]
target_dirs = dirs[1]
alns_dirs = dirs[2]
merged_dir, pdb_params_dir, replaced_params_ref_dir = dirs[3:6]
replaced_params_target_dirs = dirs[6]
complexes_dir, minimization_dir = dirs[7::]
pair_prefix = [args.ref_pdb] + args.target_pdb
pair_prefix = [e.split("/")[-1].split(".")[0] for e in pair_prefix]
pair_prefix = "_".join(pair_prefix)
# extract ligand and proteins for reference
input_pdb = args.ref_pdb
ref_filename = input_pdb.split("/")[-1].split(".")[0].split("__")[0].split("mini_")[-1]
output_ligand_pdb = f"{refs_dir}/{pair_prefix}_lig.pdb"
output_protein_pdb = f"{refs_dir}/{pair_prefix}_prot.pdb"
extract_lig_prot(input_pdb, output_ligand_pdb, output_protein_pdb)
# convert ligands to sdf for reference
input_pdb = output_ligand_pdb
output_sdf = f"{refs_dir}/{pair_prefix}_lig.sdf"
cmd_convert_pdb_to_sdf(input_pdb, args.ref_params, output_sdf)
input_target_sdfs = []
for i, tpdb in enumerate(args.target_pdb):
# extract ligand and proteins for target
input_pdb = tpdb
filename = input_pdb.split("/")[-1].split(".")[0].split("__")[0].split("mini_")[-1]
output_ligand_pdb = f"{target_dirs[i]}/{pair_prefix}_lig.pdb"
output_protein_pdb = f"{target_dirs[i]}/{pair_prefix}_prot.pdb"
extract_lig_prot(input_pdb, output_ligand_pdb, output_protein_pdb)
# convert ligands to sdf for target
input_pdb = output_ligand_pdb
output_sdf = f"{target_dirs[i]}/{pair_prefix}_lig.sdf"
cmd_convert_pdb_to_sdf(input_pdb, args.target_params[i], output_sdf)
# align ligands to reference
input_ref_sdf = f"{refs_dir}/{pair_prefix}_lig.sdf"
input_target_sdf = f"{target_dirs[i]}/{pair_prefix}_lig.sdf"
output_sdf = f"{alns_dirs[i]}/{pair_prefix}.sdf"
alignment(input_ref_sdf, input_target_sdf, args.substructure, output_sdf)
input_target_sdfs.append(input_target_sdf)
# merging to one compound
input_ref_sdf = input_ref_sdf
input_ref_sdf_filename = input_ref_sdf.split("/")[-1].split("_lig")[0]
input_target_sdfs = [f"alns_R{i+2}/{pair_prefix}.sdf" for i,f in enumerate(input_target_sdfs)]
output_sdf = f"{merged_dir}/{pair_prefix}.sdf"
merging(input_ref_sdf, input_target_sdfs, args.substructure, output_sdf)
# charge assignment
input_sdf = output_sdf
compound_filename = output_sdf.split("/")[-1].split(".")[0]
output_mol2 = f"{merged_dir}/{compound_filename}.mol2"
cmd_am1bcc_charge(input_sdf, output_mol2)
# Rosetta's param file generation
input_mol2 = output_mol2
output_prefix = f"{pdb_params_dir}/{compound_filename}"
cmd_params(input_mol2, output_prefix)
# Replace params for reference
input_ref_pdb = f"{refs_dir}/{pair_prefix}_lig.pdb"
input_ref_params = args.ref_params
input_pdb = f"{output_prefix}_0001.pdb"
input_params = f"{output_prefix}.params"
output_params = f"{replaced_params_ref_dir}/{compound_filename}.params"
cmd_replace_params(input_ref_pdb, input_ref_params, input_pdb, input_params, output_params)
for i, tpdb in enumerate(args.target_pdb):
# replace params for targets
input_ref_pdb = f"{target_dirs[i]}/{pair_prefix}_lig.pdb"
input_ref_params = args.target_params[i]
input_pdb = f"{output_prefix}_0001.pdb"
input_params = output_params
output_params = f"{replaced_params_target_dirs[i]}/{compound_filename}.params"
cmd_replace_params(input_ref_pdb, input_ref_params, input_pdb, input_params, output_params)
# concat ligand and target protein structure
protein = f"{refs_dir}/{pair_prefix}_prot.pdb"
protein_name = protein.split("/")[-1].split("_R2")[0]
input_pdb = f"{output_prefix}_0001.pdb"
output_pdb = f"{complexes_dir}/{compound_filename}__{protein_name}.pdb"
cmd_concat(protein, input_pdb, output_pdb)
# minimization of protein-ligand complex
input_pdb = output_pdb
input_params = output_params
input_klifs = args.klifs_seq
output_pdb = f"{minimization_dir}/mini_{compound_filename}__{protein_name}.pdb"
output_log = f"{minimization_dir}/mini_{compound_filename}__{protein_name}.log"
cmd_minimization(input_pdb, input_params, input_klifs, output_pdb, output_log)