[Rdkit-discuss] Conformer generation

[Paul H. <pha...@ey...>]

Hello,


I have run into a problem with using the RDKit to generate conformers of molecules. I am using the following code:


from rdkit import Chem
from rdkit.Chem import AllChem

from timeit import default_timer as timer



def GenerateDGConfs(m,num_confs,rms):
    start_time = timer()
    ids = AllChem.EmbedMultipleConfs(m, numConfs=num_confs, pruneRmsThresh=rms, maxAttempts=200,enforceChirality=True)
    for id in ids:
        AllChem.MMFFOptimizeMolecule(m, confId=id)

    end_time = timer()
    time_diff = end_time - start_time
#    print ("Normal DG = %0.2f" % time_diff)

    return m, list(ids), time_diff


w = Chem.SDWriter("%s/%s" % (rootdir,"My_conformers.sdf))


suppl = Chem.SDMolSupplier("%s/%s" % (rootdir,"My_molecules.sdf"))
num_confs = 200
rmsd = 0.5

for mol in suppl:

    if mol is None: continue

    Chem.AssignAtomChiralTagsFromStructure(mol)
    mol1 = Chem.AddHs(mol)

    conf_mol, id_list, time_diff = GenerateDGConfs(mol1,num_confs,rmsd)
    num_confs = conf_mol.GetNumConformers()
    for id in id_list:
        w.write(conf_mol, confId=id)



w.flush()
w.close()


What I see from this is as I go through the molecules in the input file the number of conformers returned declines monotonically, starting close to the 200 I set as a maximum to around 10 after a few thousand molecules have been processed (this applies whether I use 'normal' DG or the ETKDG method. As I am a new user of RDKit I am sure I missed something obvious but I cannot see it.

Also, once I generate the conformers what is best way to cluster them by RMSD so that each conformer has a minimum RMSD to all the others in the set?


Any help would be gratefully received.



Paul.