├── LICENSE ├── README.md ├── data └── test_input.smi ├── genConf.py ├── smi2sdf.py └── test.sh /LICENSE: -------------------------------------------------------------------------------- 1 | GNU GENERAL PUBLIC LICENSE 2 | Version 3, 29 June 2007 3 | 4 | Copyright (C) 2007 Free Software Foundation, Inc. 5 | Everyone is permitted to copy and distribute verbatim copies 6 | of this license document, but changing it is not allowed. 7 | 8 | Preamble 9 | 10 | The GNU General Public License is a free, copyleft license for 11 | software and other kinds of works. 12 | 13 | The licenses for most software and other practical works are designed 14 | to take away your freedom to share and change the works. By contrast, 15 | the GNU General Public License is intended to guarantee your freedom to 16 | share and change all versions of a program--to make sure it remains free 17 | software for all its users. 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It is safest 630 | to attach them to the start of each source file to most effectively 631 | state the exclusion of warranty; and each file should have at least 632 | the "copyright" line and a pointer to where the full notice is found. 633 | 634 | 635 | Copyright (C) 636 | 637 | This program is free software: you can redistribute it and/or modify 638 | it under the terms of the GNU General Public License as published by 639 | the Free Software Foundation, either version 3 of the License, or 640 | (at your option) any later version. 641 | 642 | This program is distributed in the hope that it will be useful, 643 | but WITHOUT ANY WARRANTY; without even the implied warranty of 644 | MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the 645 | GNU General Public License for more details. 646 | 647 | You should have received a copy of the GNU General Public License 648 | along with this program. If not, see . 649 | 650 | Also add information on how to contact you by electronic and paper mail. 651 | 652 | If the program does terminal interaction, make it output a short 653 | notice like this when it starts in an interactive mode: 654 | 655 | Copyright (C) 656 | This program comes with ABSOLUTELY NO WARRANTY; for details type `show w'. 657 | This is free software, and you are welcome to redistribute it 658 | under certain conditions; type `show c' for details. 659 | 660 | The hypothetical commands `show w' and `show c' should show the appropriate 661 | parts of the General Public License. Of course, your program's commands 662 | might be different; for a GUI interface, you would use an "about box". 663 | 664 | You should also get your employer (if you work as a programmer) or school, 665 | if any, to sign a "copyright disclaimer" for the program, if necessary. 666 | For more information on this, and how to apply and follow the GNU GPL, see 667 | . 668 | 669 | The GNU General Public License does not permit incorporating your program 670 | into proprietary programs. If your program is a subroutine library, you 671 | may consider it more useful to permit linking proprietary applications with 672 | the library. If this is what you want to do, use the GNU Lesser General 673 | Public License instead of this License. But first, please read 674 | . 675 | -------------------------------------------------------------------------------- /README.md: -------------------------------------------------------------------------------- 1 | # smi2sdf3d 2 | 3D diverse conformers generation using rdkit 3 | 4 | Algorithm and parameters come from: 5 | 6 | @article{DBLP:journals/jcisd/EbejerMD12, 7 | author = {Jean{-}Paul Ebejer and Garrett M. Morris and 8 | Charlotte M. Deane}, 9 | title = {Freely Available Conformer Generation Methods: 10 | How Good Are They?}, 11 | journal = {Journal of Chemical Information and Modeling}, 12 | volume = {52}, 13 | number = {5}, 14 | pages = {1146--1158}, 15 | year = {2012}, 16 | url = {https://doi.org/10.1021/ci2004658}, 17 | doi = {10.1021/ci2004658}, 18 | } 19 | -------------------------------------------------------------------------------- /data/test_input.smi: -------------------------------------------------------------------------------- 1 | C(C)O ethanol 2 | P(O)(O)(O)OP(O)(O)OP(O)(O)OC[C@H]1O[C@H]([C@@H]([C@@H]1O)O)[n+]1c[nH]c2c(N)ncnc12 ATP 3 | -------------------------------------------------------------------------------- /genConf.py: -------------------------------------------------------------------------------- 1 | #!/usr/bin/env python3 2 | # ---------------------------------------------------------- 3 | # Copyright (C) 2017 PHARAMACELERA S.L. 4 | # All rights reserved. 5 | # 6 | # WARRANTY DISCLAIMER 7 | # 8 | # THESE MATERIALS ARE PROVIDED BY THE COPYRIGHT HOLDERS AND CONTRIBUTORS 9 | # "AS IS" AND ANY EXPRESS OR IMPLIED WARRANTIES, INCLUDING, BUT NOT 10 | # LIMITED TO, THE IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR 11 | # A PARTICULAR PURPOSE ARE DISCLAIMED. IN NO EVENT SHALL PHARMACELERA OR ITS 12 | # CONTRIBUTORS BE LIABLE FOR ANY DIRECT, INDIRECT, INCIDENTAL, SPECIAL, 13 | # EXEMPLARY, OR CONSEQUENTIAL DAMAGES (INCLUDING, BUT NOT LIMITED TO, 14 | # PROCUREMENT OF SUBSTITUTE GOODS OR SERVICES; LOSS OF USE, DATA, OR 15 | # PROFITS; OR BUSINESS INTERRUPTION) HOWEVER CAUSED AND ON ANY THEORY 16 | # OF LIABILITY, WHETHER IN CONTRACT, STRICT LIABILITY OR TORT (INCLUDING 17 | # NEGLIGENCE OR OTHERWISE) ARISING IN ANY WAY OUT OF THE USE OF THESE 18 | # MATERIALS, EVEN IF ADVISED OF THE POSSIBILITY OF SUCH DAMAGE. 19 | # 20 | # File: genConf.py 21 | # 22 | # Created on 19/07/2017 23 | # Last update 29/11/2021 24 | # ---------------------------------------------------------- 25 | # 26 | # Molecular conformer generator 27 | # 28 | # Example: 29 | # 30 | # genConf.py -i file_input.sdf -o file_output.sdf 31 | # -n number_of_conformers (optional, if not specified is based 32 | # on the nomber of rotable bonds) -rms rms_threshold 33 | # -e energy_window (optional, Kcal/mol) -t number_of_threads (if not specify 1) 34 | # -ETKDG (optional, use the useExpTorsionAnglePrefs and useBasicKnowledge options) 35 | # -logfile (Default: False, write a log file with info about the conformer generation) 36 | # ---------------------------------------------------------- 37 | # ---------------------------------------------------------- 38 | import sys 39 | from rdkit import Chem 40 | from rdkit.Chem import AllChem 41 | from rdkit import RDLogger 42 | from concurrent import futures 43 | import progressbar 44 | import argparse 45 | import copy 46 | import time 47 | import gzip 48 | 49 | def genConf(m, nc, rms, efilter, rmspost, nmol, molName, etkdg): 50 | mini=None 51 | info = "" 52 | nr = int(AllChem.CalcNumRotatableBonds(m)) 53 | m4 = copy.deepcopy(m) 54 | m = Chem.AddHs(m) 55 | Chem.AssignAtomChiralTagsFromStructure(m, replaceExistingTags=True) 56 | Chem.AssignStereochemistry(m, cleanIt=True, force=True) 57 | doublestereolist=[] 58 | for b in range(0, m.GetNumBonds()): 59 | st = str(m.GetBondWithIdx(b).GetStereo()) 60 | ty = str(m.GetBondWithIdx(b).GetBondType()) 61 | if ty == "DOUBLE" and (st == 'STEREOZ' or st == "STEREOCIS"): 62 | doublestereolist.append((b, "STEREO Z")) 63 | elif ty == "DOUBLE" and (st == "STEREOE" or st == "STEREOTRANS"): 64 | doublestereolist.append((b, "STEREO E")) 65 | Chem.AssignStereochemistry(m, cleanIt=True, flagPossibleStereoCenters=True) 66 | chiralcenter = Chem.FindMolChiralCenters(m)+doublestereolist 67 | if nc == "X": 68 | if nr < 3: 69 | nc = 50 70 | elif nr > 6: 71 | nc = 300 72 | else: 73 | nc = nr**3 74 | m3 = copy.deepcopy(m) 75 | m5 = copy.deepcopy(m) 76 | ids=AllChem.EmbedMultipleConfs(m, numConfs=nc, pruneRmsThresh=rms, randomSeed=1, useExpTorsionAnglePrefs=etkdg, useBasicKnowledge=etkdg) 77 | if rms == -1 and efilter == "Y": 78 | if len(ids) != nc: 79 | info = "WARNING: " + molName + " generated less molecules than those required\n" 80 | numconf = m.GetNumConformers() 81 | if numconf == 0: 82 | m = copy.deepcopy(m3) 83 | ids=AllChem.EmbedMultipleConfs(m, numConfs=nc, pruneRmsThresh=rms, randomSeed=1) 84 | info = "WARNING: Molecule number " + str(nmol) + " embed without ETKDG method, molecule name: " + molName + "\n" 85 | m2 = copy.deepcopy(m) 86 | diz = [] 87 | diz2 = [] 88 | diz3 = [] 89 | if m.GetNumConformers() == 0: 90 | info = "ERROR: Impossible to generate conformers of molecule " + str(nmol) + ", molecule name: " + molName + "\n" 91 | o = m4 92 | o = Chem.AddHs(o) 93 | embd = AllChem.EmbedMolecule(o, randomSeed=1) 94 | if embd == -1: 95 | info = "ERROR: Impossible to generate conformers of molecule " + str(nmol) + ", molecule name: " + molName + "\n" 96 | o = m4 97 | diz3 = [(None, -1)] 98 | 99 | else: 100 | for id in ids: 101 | molec = m.GetConformer(id).GetOwningMol() 102 | doublestereolist=[] 103 | for b in range(0, molec.GetNumBonds()): 104 | st = str(molec.GetBondWithIdx(b).GetStereo()) 105 | ty = str(molec.GetBondWithIdx(b).GetBondType()) 106 | if ty == "DOUBLE" and (st == 'STEREOZ' or st == "STEREOCIS"): 107 | doublestereolist.append((b, "STEREO Z")) 108 | elif ty == "DOUBLE" and (st == "STEREOE" or st == "STEREOTRANS"): 109 | doublestereolist.append((b, "STEREO E")) 110 | Chem.AssignStereochemistry(molec, cleanIt=True, flagPossibleStereoCenters=True) 111 | confchiralcenter = Chem.FindMolChiralCenters(molec)+doublestereolist 112 | if confchiralcenter != chiralcenter: 113 | m.RemoveConformer(id) 114 | if m.GetNumConformers() == 0: 115 | m = m5 116 | ids=AllChem.EmbedMultipleConfs(m, numConfs=nc, pruneRmsThresh=rms, randomSeed=1) 117 | for id in ids: 118 | molec = m.GetConformer(id).GetOwningMol() 119 | for b in range(0, molec.GetNumBonds()): 120 | st = str(molec.GetBondWithIdx(b).GetStereo()) 121 | ty = str(molec.GetBondWithIdx(b).GetBondType()) 122 | if ty == "DOUBLE" and (st == 'STEREOZ' or st == "STEREOCIS"): 123 | doublestereolist.append((b, "STEREO Z")) 124 | elif ty == "DOUBLE" and (st == "STEREOE" or st == "STEREOTRANS"): 125 | doublestereolist.append((b, "STEREO E")) 126 | Chem.AssignStereochemistry(molec, cleanIt=True, flagPossibleStereoCenters=True) 127 | confchiralcenter = Chem.FindMolChiralCenters(molec)+doublestereolist 128 | if confchiralcenter != chiralcenter: 129 | if info != "": 130 | info = info + "\n" 131 | info = "WARNING: one or more conformer of Molecule number " + str(nmol) + " were excluded becouse it/they has/have different isomerism respect the input: " + molName + "\n" 132 | m.RemoveConformer(id) 133 | try: 134 | if AllChem.MMFFHasAllMoleculeParams(m) == True: 135 | sm = copy.deepcopy(m) 136 | try: 137 | for id in ids: 138 | prop = AllChem.MMFFGetMoleculeProperties(m, mmffVariant="MMFF94s") 139 | ff = AllChem.MMFFGetMoleculeForceField(m, prop, confId=id) 140 | ff.Minimize() 141 | en = float(ff.CalcEnergy()) 142 | econf = (en, id) 143 | diz.append(econf) 144 | except: 145 | m = sm 146 | for id in ids: 147 | ff = AllChem.UFFGetMoleculeForceField(m, confId=id) 148 | ff.Minimize() 149 | en = float(ff.CalcEnergy()) 150 | econf = (en, id) 151 | diz.append(econf) 152 | if info != "": 153 | info = info + "WARNING: Molecule number " + str(nmol) + " optimized with UFF force field, molecule name: " + molName + "\n" 154 | else: 155 | info = "WARNING: Molecule number " + str(nmol) + " optimized with UFF force field, molecule name: " + molName + "\n" 156 | else: 157 | for id in ids: 158 | ff = AllChem.UFFGetMoleculeForceField(m, confId=id) 159 | ff.Minimize() 160 | en = float(ff.CalcEnergy()) 161 | econf = (en, id) 162 | diz.append(econf) 163 | if info != "": 164 | info = info + "WARNING: Molecule number " + str(nmol) + " optimized with UFF force field, molecule name: " + molName + "\n" 165 | else: 166 | info = "WARNING: Molecule number " + str(nmol) + " optimized with UFF force field, molecule name: " + molName + "\n" 167 | except: 168 | m = m2 169 | if info != "": 170 | info = info + "ERROR: Unable to minimize molecule number: " + str(nmol)+ ", molecule name: " + molName + "\n" 171 | else: 172 | info = "ERROR: Unable to minimize molecule number: " + str(nmol)+ ", molecule name: " + molName + "\n" 173 | for id in ids: 174 | en = None 175 | econf = (en, id) 176 | diz.append(econf) 177 | 178 | if efilter != "Y": 179 | n, diz2, mini = ecleaning(m, diz, efilter) 180 | else: 181 | n = m 182 | diz2 = copy.deepcopy(diz) 183 | diz.sort() 184 | mini = float(diz[0][0]) 185 | mini 186 | if rmspost != False and n.GetNumConformers() > 1: 187 | o, diz3 = postrmsd(n, diz2, rmspost) 188 | else: 189 | o = n 190 | diz3 = diz2 191 | 192 | return o, diz3, nr, info, mini 193 | 194 | def ecleaning(m, diz, efilter): 195 | diz.sort() 196 | mini = float(diz[0][0]) 197 | sup = mini + efilter 198 | n = Chem.Mol(m) 199 | n.RemoveAllConformers() 200 | n.AddConformer(m.GetConformer(int(diz[0][1]))) 201 | diz2=[[float(diz[0][0]), int(diz[0][1])]] 202 | del diz[0] 203 | for x,y in diz: 204 | if x <= sup: 205 | n.AddConformer(m.GetConformer(int(y))) 206 | uni = [float(x), int(y)] 207 | diz2.append(uni) 208 | else: 209 | break 210 | return n, diz2, mini 211 | 212 | def postrmsd(n, diz2, rmspost): 213 | diz2.sort() 214 | o = Chem.Mol(n) 215 | o.RemoveAllConformers() 216 | confidlist = [diz2[0][1]] 217 | enval = [diz2[0][0]] 218 | nh = Chem.RemoveHs(n) 219 | nh = Chem.DeleteSubstructs(nh, Chem.MolFromSmiles('F')) 220 | nh = Chem.DeleteSubstructs(nh, Chem.MolFromSmiles('Br')) 221 | nh = Chem.DeleteSubstructs(nh, Chem.MolFromSmiles('Cl')) 222 | nh = Chem.DeleteSubstructs(nh, Chem.MolFromSmiles('I')) 223 | del diz2[0] 224 | for z,w in diz2: 225 | confid = int(w) 226 | p=0 227 | for conf2id in confidlist: 228 | rmsd = AllChem.GetBestRMS(nh, nh, prbId=confid, refId=conf2id) 229 | if rmsd < rmspost: 230 | p=p+1 231 | break 232 | if p == 0: 233 | confidlist.append(int(confid)) 234 | enval.append(float(z)) 235 | for id in confidlist: 236 | o.AddConformer(n.GetConformer(id)) 237 | diz3 = zip(enval, confidlist) 238 | return o, diz3 239 | 240 | #----------------------------------- Main function -------------------------------------- 241 | if __name__ == "__main__": 242 | parser = argparse.ArgumentParser(description='Molecular conformer generator') 243 | parser.add_argument('-i', required=True, help='sdf input file') 244 | parser.add_argument('-o', required=True, help='sdf output file') 245 | parser.add_argument('-n', type=int, required=False, help='number of conformers') 246 | parser.add_argument('-rms', type=float, required=False, help='rms threshold pre optimization') 247 | parser.add_argument('-e', type=float, required=False, help='energy window') 248 | parser.add_argument('-notprintproperty', action='store_true', help='Print molecule properties (energy and rotable bond number)') 249 | parser.add_argument('-ETKDG', action='store_true', help='use the useExpTorsionAnglePrefs and useBasicKnowledge options') 250 | parser.add_argument('-logfile', action='store_true', help='write a log file') 251 | parser.add_argument('-t', type=int, required=False, help='number of threads') 252 | args = parser.parse_args() 253 | lg = RDLogger.logger() 254 | lg.setLevel(RDLogger.CRITICAL) 255 | time_start = time.time() 256 | inp = args.i 257 | out = args.o 258 | 259 | if args.rms == None: 260 | rmspre = -1 261 | else: 262 | rmspre = args.rms 263 | if args.rms == None: 264 | rmspost = False 265 | irmsd = "Not" 266 | else: 267 | rmspost = args.rms 268 | irmsd = str(args.rms) + " A" 269 | if args.t == None: 270 | threads = 1 271 | else: 272 | threads = args.t 273 | if args.e == None: 274 | ent = "Y" 275 | iener = "Not" 276 | else: 277 | ent = args.e 278 | iener = str(args.e)+" Kcal/mol" 279 | if args.n==None: 280 | nc = "X" 281 | inc = "Rotatable bond based" 282 | else: 283 | nc = args.n 284 | inc = str(args.n) 285 | etkdg = False 286 | etkdginfo = "Not" 287 | if args.ETKDG == True: 288 | etkdg = True 289 | etkdginfo = "Yes" 290 | 291 | writer = Chem.SDWriter(out) 292 | 293 | if inp.endswith(".sdf"): 294 | suppl = Chem.SDMolSupplier(inp) 295 | elif inp.endswith(".gz"): 296 | inp = gzip.open(inp) 297 | suppl = Chem.ForwardSDMolSupplier(inp) 298 | 299 | totmol = len(suppl) 300 | 301 | ##log file## 302 | if args.logfile == True: 303 | log = open(out.replace(".sdf", ".log"), "w") 304 | log.write("Conformer generator\nTotal molecule number: " + str(totmol) + "\nEnergy filter: " + iener + "\nRMSD filter: " + irmsd + "\nETKDG method: " + etkdginfo + "\nNumber of conformers per molecule: " + inc + "\nNumber of threads: "+str(threads)+"\n\n") 305 | ncicle = (totmol//1000) 306 | numMol = 0 307 | NM = [] 308 | with futures.ProcessPoolExecutor(max_workers=threads) as executor: 309 | start = 0 310 | if totmol <= 999: 311 | end = totmol-1 312 | else: 313 | end = 999 314 | for cicle in range(0, ncicle+1): 315 | info = "" 316 | jobs = [] 317 | nm = [] 318 | for sup in range(start,end+1): 319 | numMol = numMol+1 320 | mol = suppl[sup] 321 | if mol is not None: 322 | NM.append(numMol) 323 | molName = mol.GetProp('_Name') 324 | nm.append(molName) 325 | job = executor.submit(genConf, mol, nc, rmspre, ent, rmspost, numMol, molName, etkdg) 326 | jobs.append(job) 327 | else: 328 | info = "ERROR: Impossible read " + str(numMol) 329 | if args.logfile == True: 330 | log.write(info+ "\n") 331 | widgets = ["Generating conformations of molecules from " + str(start+1) + " to " + str(end+1) +"; " , progressbar.Percentage(), " ", progressbar.ETA(), " ", progressbar.Bar()] 332 | pbar = progressbar.ProgressBar(widgets=widgets, maxval=len(jobs)) 333 | for job in pbar(futures.as_completed(jobs)): 334 | mol,ids,nr,info,mini = job.result() 335 | for j in range(0, len(jobs)): 336 | mol,ids,nr,info,mini = jobs[j].result() 337 | name = nm[j] 338 | propDic = suppl[NM[j+start]-1].GetPropsAsDict() 339 | if info != "": 340 | mol.SetProp('genConf_Info', info) 341 | if args.logfile == True: 342 | log.write(info) 343 | for en,id in ids: 344 | mol.SetProp('_Name', name) 345 | if args.notprintproperty == False: 346 | for k in propDic: 347 | mol.SetProp(k, str(propDic[k])) 348 | if en == None: 349 | mol.SetProp('CONF_ENERGY', "Unable to calculate") 350 | else: 351 | mol.SetProp('CONF_ENERGY', str(en)+ " Kcal/mol") 352 | if mini != en: 353 | mol.SetProp('ENERGY_DIFFERENCE', str(en-mini)+ " Kcal/mol") 354 | else: 355 | mol.SetProp('ENERGY_DIFFERENCE', "0.00 Kcal/mol") 356 | mol.SetProp('RotatableBondsNumber', str(nr)) 357 | if args.logfile == False and info != "": 358 | print(info.replace('\n','')) 359 | if not "ERROR: Impossible to generate conformers of molecule " in info: 360 | writer.write(mol, confId=id) 361 | start = start + 1000 362 | if cicle == ncicle -1: 363 | end = totmol-1 364 | else: 365 | end = end + 1000 366 | if end == sup: 367 | break 368 | writer.close() 369 | time_end = time.time() 370 | exTime = time_end - time_start 371 | if args.logfile == True: 372 | log.write("Execution time " + str(exTime) + " seconds") 373 | log.close() 374 | -------------------------------------------------------------------------------- /smi2sdf.py: -------------------------------------------------------------------------------- 1 | #!/usr/bin/env python3 2 | 3 | # generation of up to N low energy conformers 4 | # from 2D input (smi) to 3D output (sdf) 5 | # see Ebejer et. al. 6 | # "Freely Available Conformer Generation Methods: How Good Are They?" 7 | # JCIM, 2012, DOI: 10.1021/ci2004658 for technical details 8 | # 9 | # Copyright (C) 2018 Francois Berenger 10 | # System Cohort Division, 11 | # Medical Institute of Bioregulation, 12 | # Kyushu University 13 | # 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan 14 | # 15 | # This program is free software: you can redistribute it and/or modify 16 | # it under the terms of the GNU General Public License as published by 17 | # the Free Software Foundation, either version 3 of the License, or 18 | # (at your option) any later version. 19 | # 20 | # This program is distributed in the hope that it will be useful, 21 | # but WITHOUT ANY WARRANTY; without even the implied warranty of 22 | # MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the 23 | # GNU General Public License for more details. 24 | # 25 | # You should have received a copy of the GNU General Public License 26 | # along with this program. If not, see . 27 | 28 | from __future__ import print_function 29 | 30 | import argparse 31 | import multiprocessing as mp 32 | import rdkit 33 | import sys 34 | from contextlib import closing 35 | from rdkit import Chem 36 | from rdkit.Chem import AllChem, rdMolAlign 37 | 38 | def RobustSmilesMolSupplier(filename): 39 | with open(filename) as f: 40 | for line in f: 41 | words = line.split() 42 | smile = words[0] 43 | name = words[1] 44 | yield name, Chem.MolFromSmiles(smile) 45 | 46 | # nb. conformers to generate prior to energy minimization 47 | # as an empirical function of the molecule's flexibility 48 | def how_many_conformers(mol): 49 | nb_rot_bonds = AllChem.CalcNumRotatableBonds(mol) 50 | if nb_rot_bonds <= 7: 51 | return 50 52 | elif nb_rot_bonds <= 12: 53 | return 200 54 | return 300 # This is more 55 | 56 | # keep only conformers which are far enough from the reference conformer 57 | def rmsd_filter(mol, ref_conf, conf_energies, threshold): 58 | # we use heavy atoms RMSD; not all atoms (Peter Gedeck's suggestion) 59 | mol_noH = Chem.RemoveHs(mol) 60 | ref_conf_id = ref_conf.GetId() 61 | res = [] 62 | for e, curr_conf in conf_energies: 63 | curr_conf_id = curr_conf.GetId() 64 | rms = AllChem.GetConformerRMS(mol_noH, ref_conf_id, curr_conf_id) 65 | if rms > threshold: 66 | res.append((e, curr_conf)) 67 | return res 68 | 69 | def process_one(name, mol, n_confs): 70 | n = how_many_conformers(mol) 71 | print("init pool size for %s: %d" % (name, n), file = sys.stderr) 72 | mol_H = Chem.AddHs(mol) 73 | res = Chem.Mol(mol_H) 74 | res.RemoveAllConformers() 75 | print("generating starting conformers ...", file = sys.stderr) 76 | conf_energies = [] 77 | print("FF minimization ...", file = sys.stderr) 78 | for cid in AllChem.EmbedMultipleConfs(mol_H, n): 79 | ff = AllChem.UFFGetMoleculeForceField(mol_H, confId = cid) 80 | # print("E before: %f" % ff.CalcEnergy()) 81 | ff.Minimize() 82 | energy = ff.CalcEnergy() 83 | # print("E after: %f" % energy) 84 | conformer = mol_H.GetConformer(cid) 85 | # print("cid: %d e: %f" % (cid, energy)) 86 | conf_energies.append((energy, conformer)) 87 | # sort by increasing E 88 | conf_energies = sorted(conf_energies, key = lambda x: x[0]) 89 | # output non neighbor conformers 90 | kept = 0 91 | print("RMSD pruning ...", file = sys.stderr) 92 | while kept < n_confs and len(conf_energies) > 0: 93 | (e, conf) = conf_energies.pop(0) 94 | kept += 1 95 | cid = res.AddConformer(conf, assignId = True) 96 | # align conformers to the one of lowest energy 97 | if cid != 0: 98 | rdMolAlign.AlignMol(res, res, prbCid = cid, refCid = 0) 99 | # remove neighbors 100 | conf_energies = rmsd_filter(mol_H, conf, conf_energies, rmsd_threshold) 101 | print("kept %d confs for %s" % (kept, name), file = sys.stderr) 102 | name_res = (name, res) 103 | #res.SetProp("_Name", name) # !!! not working !!! 104 | return name_res 105 | 106 | def worker_process(jobs_q, results_q, n_confs): 107 | for name, mol in iter(jobs_q.get, 'STOP'): 108 | confs = process_one(name, mol, n_confs) 109 | results_q.put(confs) 110 | # tell the multiplexer I am done 111 | results_q.put('STOP') 112 | 113 | def write_out_confs(rename, name_confs, writer): 114 | name, confs = name_confs 115 | for c in confs.GetConformers(): 116 | cid = c.GetId() 117 | if rename: 118 | # append conformer id to molecule name 119 | name_cid = "%s_%03d" % (name, cid) 120 | # the following renames the molecule, but we have no choice 121 | confs.SetProp("_Name", name_cid) 122 | else: 123 | confs.SetProp("_Name", name) 124 | writer.write(confs, confId = cid) 125 | 126 | def multiplexer_process(rename, results_q, output_sdf, nb_workers): 127 | with closing(Chem.SDWriter(output_sdf)) as writer: 128 | for i in range(nb_workers): 129 | for confs in iter(results_q.get, 'STOP'): 130 | write_out_confs(rename, confs, writer) 131 | 132 | if __name__ == '__main__': 133 | # to prune too similar conformers 134 | rmsd_threshold = 0.35 # Angstrom 135 | # CLI parsing setup 136 | parser = argparse.ArgumentParser( 137 | description = "generate diverse low energy 3D conformers; \ 138 | up to [n_confs] per molecule from the input file") 139 | parser.add_argument("-n", metavar = "n_confs", type = int, default = 1, 140 | dest = "n_confs", 141 | help = "#conformers per molecule (default: 1)") 142 | parser.add_argument("-j", metavar="n_procs", type = int, default = 1, 143 | dest = "n_procs", 144 | help = "max number of parallel jobs (default: 1)") 145 | parser.add_argument("-i", metavar = "input_smi", dest = "input_smi") 146 | parser.add_argument("-o", metavar = "output_sdf", dest = "output_sdf") 147 | parser.add_argument('--rename', dest='rename', action='store_true', 148 | help = "append conformer id to molecule name \ 149 | (default=False") 150 | parser.set_defaults(rename=False) 151 | # parse CLI 152 | # show help in case user has no clue of what to do 153 | if len(sys.argv) == 1: 154 | parser.print_help(sys.stderr) 155 | sys.exit(1) 156 | args = parser.parse_args() 157 | n_confs = args.n_confs 158 | input_smi = args.input_smi 159 | output_sdf = args.output_sdf 160 | n_procs = args.n_procs # for parallelization 161 | rename = args.rename 162 | if n_procs > 1: 163 | # process molecules in parallel 164 | # multiprocessing queues 165 | jobs_queue = mp.Queue() 166 | results_queue = mp.Queue() 167 | # start workers 168 | # print('starting workers') 169 | for i in range(n_procs): 170 | mp.Process(target = worker_process, 171 | args = (jobs_queue, results_queue, n_confs)).start() 172 | # start the multiplexer 173 | # print('starting multiplexer') 174 | mp.Process(target = multiplexer_process, 175 | args = (rename, results_queue, output_sdf, n_procs)).start() 176 | # feed workers 177 | # print('feeding workers') 178 | for name, mol in RobustSmilesMolSupplier(input_smi): 179 | if mol is None: 180 | continue 181 | jobs_queue.put((name, mol)) 182 | # tell workers that no more jobs will come 183 | for i in range(n_procs): 184 | jobs_queue.put('STOP') 185 | # print('no more jobs') 186 | else: 187 | # process molecules sequentially 188 | with closing(Chem.SDWriter(output_sdf)) as writer: 189 | for name, mol in RobustSmilesMolSupplier(input_smi): 190 | if mol is None: 191 | continue 192 | conformers = process_one(name, mol, n_confs) 193 | write_out_confs(rename, conformers, writer) 194 | -------------------------------------------------------------------------------- /test.sh: -------------------------------------------------------------------------------- 1 | #!/bin/bash 2 | 3 | out=data/test_output.sdf 4 | 5 | \rm -f ${out} 6 | 7 | ./smi2sdf.py -n 10 -i data/test_input.smi -o ${out} 8 | 9 | echo '#molecules in output:' 10 | which molcount 2>&1 >/dev/null && molcount ${out} 11 | --------------------------------------------------------------------------------