| # -*- coding: utf-8 -*- | |
| # The B3clf library computes the blood-brain barrier (BBB) permeability | |
| # of organic molecules with resampling strategies. | |
| # | |
| # Copyright (C) 2021 The Ayers Lab | |
| # | |
| # This file is part of B3clf. | |
| # | |
| # B3clf is free software; you can redistribute it and/or | |
| # modify it under the terms of the GNU General Public License | |
| # as published by the Free Software Foundation; either version 3 | |
| # of the License, or (at your option) any later version. | |
| # | |
| # B3clf is distributed in the hope that it will be useful, | |
| # but WITHOUT ANY WARRANTY; without even the implied warranty of | |
| # MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the | |
| # GNU General Public License for more details. | |
| # | |
| # You should have received a copy of the GNU General Public License | |
| # along with this program; if not, see <http://www.gnu.org/licenses/> | |
| # | |
| # -- | |
| import pandas as pd | |
| from rdkit import Chem | |
| from rdkit.Chem import AllChem | |
| """Convert SMILES to 3D and/or minimize the geometry from SDF with force field.""" | |
| def geometry_optimize(input_fname, | |
| output_sdf, | |
| steps_opt=10000, | |
| # convergence=1.e-7, | |
| tool="rdkit", | |
| # optimization="cg", | |
| force_field="MMFF94s", | |
| smi_col=None, | |
| sep="\s+|t+"): | |
| """Generate 3D coordinates and run geometry optimization with force field.""" | |
| # optimize the 3d coordinates | |
| # use RDKit to minimize the geometry | |
| if tool.lower() == "rdkit": | |
| minimize_with_rdkit(input_molfname=input_fname, | |
| sdf_out=output_sdf, | |
| maxIters=steps_opt, | |
| force_field=force_field, | |
| smi_col=smi_col, | |
| sep=sep) | |
| # use openbabel to minimize the geometry | |
| elif tool == "openbabel": | |
| # minimize_with_openbabel(input_molfname=input_fname, | |
| # sdf_out=output_sdf, | |
| # steps=steps_opt, | |
| # optimization=optimization, | |
| # convergence=convergence, | |
| # force_field=force_field, | |
| # smi_col=smi_col) | |
| raise ValueError("OpenBabel is not supported yet.") | |
| else: | |
| raise ValueError("{} not implemented yet.".format(tool)) | |
| def minimize_with_rdkit(input_molfname, | |
| sdf_out, | |
| smi_col=None, | |
| mol_name_col=None, | |
| maxIters=400, | |
| force_field="MMFF94s", | |
| sep="\s+"): | |
| """Add hydrogen for 3D coordinates and minimize the geometry with RdKit.""" | |
| # load molecules | |
| if input_molfname.lower().endswith(".smi") or input_molfname.lower().endswith(".csv"): | |
| # todo: support .txt files | |
| # todo: add support of more flexible separators | |
| # todo: fix problem when mol_name is empty | |
| df_mol = pd.read_csv(input_molfname, sep=sep, engine="python", header=None) | |
| if df_mol.shape[1] == 1: | |
| # Case for only SMILES column | |
| smile_list = df_mol.iloc[:, -1].to_list() | |
| mol_name_list = df_mol.iloc[:, -1].to_list() | |
| else: | |
| # Case for SMILES and MOL name columns | |
| if smi_col is None: | |
| smile_list = df_mol.iloc[:, 0].to_list() | |
| else: | |
| smile_list = df_mol[smi_col].to_list() | |
| if mol_name_col is None: | |
| # todo: use name if column name is valid | |
| mol_name_list = df_mol.iloc[:, -1].to_list() | |
| else: | |
| mol_name_list = df_mol[mol_name_col].to_list() | |
| mols = [] | |
| for idx, smi in enumerate(smile_list): | |
| mol = Chem.MolFromSmiles(smi) | |
| # This will overwrite | |
| if mol is not None: | |
| mol.SetProp("_Name", mol_name_list[idx]) | |
| mols.append(mol) | |
| elif input_molfname.lower().endswith(".sdf"): | |
| suppl = Chem.SDMolSupplier(input_molfname, | |
| sanitize=True, | |
| removeHs=False, | |
| strictParsing=True) | |
| mols = [mol for mol in suppl] | |
| for idx, mol in enumerate(mols): | |
| if (mol.GetProp("_Name") == "") or (mol.GetProp("_Name") is None): | |
| smi = Chem.MolToSmiles(mol) | |
| mol.SetProp("_Name", smi) | |
| mols[idx] = mol | |
| writer = Chem.SDWriter(sdf_out) | |
| for idx, mol in enumerate(mols): | |
| mol = Chem.AddHs(mol) | |
| if force_field == "MMFF94s": | |
| # use MMFF~ force field if possible | |
| # taken from | |
| # https://open-babel.readthedocs.io/en/latest/Forcefields/mmff94.html | |
| # Some experiments and most theoretical calculations show significant pyramidal | |
| # “puckering” at nitrogens in isolated structures. The MMFF94s (static) variant has | |
| # slightly different out-of-plane bending and dihedral torsion parameters to planarize | |
| # certain types of delocalized trigonal N atoms, such as aromatic aniline. This provides | |
| # a better match to the time-average molecular geometry in solution or crystal | |
| # structures. | |
| # | |
| # If you are comparing force-field optimized molecules to crystal structure geometries, | |
| # we recommend using the MMFF94s variant for this reason. All other parameters are | |
| # identical. However, if you are performing “docking” simulations, consideration of | |
| # active solution conformations, or other types of computational studies, we recommend | |
| # using the MMFF94 variant, since one form or another of the N geometry will | |
| # predominate. | |
| AllChem.EmbedMolecule(mol, randomSeed=999) | |
| # the following code will raise some errors | |
| mini_tag = AllChem.MMFFOptimizeMolecule(mol, force_field, maxIters=maxIters) | |
| # 0 optimize converged | |
| # -1 can not set up force field | |
| # 1 more iterations required | |
| if mini_tag == 0: | |
| writer.write(mol) | |
| else: | |
| if mini_tag == 1: | |
| AllChem.MMFFOptimizeMolecule(mol, force_field, maxIters=maxIters * 2) | |
| elif mini_tag == -1: | |
| AllChem.UFFOptimizeMolecule(mol, maxIters=400) | |
| writer.write(mol) | |
| elif force_field == "uff": | |
| # use uff force field if possible | |
| AllChem.EmbedMolecule(mol, randomSeed=999) | |
| # the following code will raise some errors | |
| mini_tag = AllChem.UFFOptimizeMolecule(mol, maxIters=maxIters) | |
| # 0 optimize converged | |
| # -1 can not set up force field | |
| # 1 more iterations required | |
| if mini_tag == 0: | |
| writer.write(mol) | |
| else: | |
| if mini_tag == 1: | |
| AllChem.UFFOptimizeMolecule(mol, maxIters=maxIters * 2) | |
| elif mini_tag == -1: | |
| AllChem.MMFFOptimizeMolecule(mol, "MMFF94s", maxIters=maxIters) | |
| writer.write(mol) | |
| else: | |
| raise NotImplementedError("This method is not implemented yet.") | |
| writer.close() | |
| # todo: now the implementation is not supporting adding molecule name (such as SMILES strings) | |
| # def minimize_with_openbabel(input_molfname, | |
| # sdf_out, | |
| # steps=10000, | |
| # convergence=1.e-7, | |
| # optimization="cg", | |
| # force_field="GAFF", | |
| # smi_col=None): | |
| # """Minimize the geometries with openbabel. | |
| # | |
| # Parameters | |
| # ---------- | |
| # input_molfname : str | |
| # Input molecule fie name. | |
| # sdf_out : str | |
| # Output molecule file name. | |
| # steps : int, optional | |
| # Specify the maximum number of steps. default=2500. | |
| # optimization : str, optional | |
| # Use conjugate gradients ("cg") or steepest descent ("sd") algorithm for optimization. | |
| # Default="cg". | |
| # convergence : float, optional | |
| # convergence threshold. Default=1.e-7. | |
| # force_field : str, optional | |
| # ForceField name including Generalized Amber Force Field (gaff), Ghemical Force Field | |
| # (ghemical), MMFF94 Force Field (mmff94) and Universal Force Field (uff). Default="gaff". | |
| # """ | |
| # | |
| # # https://open-babel.readthedocs.io/en/latest/Command-line_tools/babel.html#forcefield-energy-and-minimization | |
| # subprocess.Popen(["obabel", input_molfname, "-h", "-O", sdf_out, | |
| # "--gen3d", "--minimize", | |
| # "--n", str(steps), "--sd", optimization, "--crit", | |
| # str(convergence), "--ff", force_field]) | |
| # print("Geometry optimization with OpenBabel is done.") | |