Hi Michal, Many thanks for the help!
The MMFF will be mainly used to remove only the (very) high energy conformers, which is a good news here. There is one dilemma here: Without optimization, some potentially "good" conformers could be filted out, due to the fact that small unreasonable atomic displacements could increase the energy by a lot. With optimization, however, many different conformers will just converge to the same structure. I will probably focus on just energies, without optimization. I even tried UFF, which I found much faster than MMFF94s. Best, Leon On Thu, Dec 19, 2019 at 7:49 AM Michal Krompiec <michal.kromp...@gmail.com> wrote: > For mid-to-lower-energy conformers, MMFF relative energies are > essentially a fancy random-number generator. Still, all depends on > what you need this for. If you just want to filter out (very) high > energy conformers, your approach might work. But if you also want to > perform Boltzmann averaging over conformational ensemble (of lower > energy conformers), you will be disappointed. > BTW conformational analysis of your molecule with CREST (20 OMP > threads, -quick -norotmd) took 219 seconds and yielded 28 conformers > with energy up to 3.5 kcal/mol higher than lowest energy structure. So > it is ~2 orders of magnitude slower than MMFF. > Best, > Michal > > On Thu, 19 Dec 2019 at 03:53, topgunhaides . <sunzhi....@gmail.com> wrote: > > > > Hi Michal, > > > > Many thanks for the help! I am looking for an ensemble of conformers. > > My priority is to use RDKit to generate a large ensemble of conformers > for each molecule. > > For large and flexiable molecules, will need a lot more than 10K (like > 100K) to try to cover the entire conformational space. > > > > I do not have to use MMFF to optimize all conformers, but I do want to > use MMFF or UFF to get at least the energies of all conformers (which is > also quite time-consuming, even without optimization). > > With the conformer energies, I can call some energy_filtering function > to filter out conformers with high energies, etc. > > I am thinking that storing and processing a huge number of conformers > could be the reason to slow things down, but not quite sure. > > Any suggestions are very welcome! > > > > Best, > > Leon > > > > > > > > > > > > > > > > On Wed, Dec 18, 2019 at 7:08 PM Michal Krompiec < > michal.kromp...@gmail.com> wrote: > >> > >> Are you looking for the global minimum or an ensemble of conformers? > Either way, this is already very fast. Bear in mind, however, that MMFF’s > accuracy isn’t great for this type of tasks (see for example > >> https://arxiv.org/pdf/1705.04308.pdf ). In other words, I don’t see a > use case for generation of 10k or more conformers with MMFF. And super-fast > generation of large conformational ensembles for arbitrary molecules just > isn’t realistic. > >> Best, > >> Michal > >> > >> On Wed, 18 Dec 2019 at 22:40, topgunhaides . <sunzhi....@gmail.com> > wrote: > >>> > >>> Hi guys, > >>> > >>> Can anyone give me some advices to improve the efficiency of the > embedding code? See example below: > >>> > >>> > >>> import time > >>> from rdkit import Chem > >>> from rdkit.Chem import AllChem > >>> > >>> suppl = Chem.SDMolSupplier('cid831548.sdf') # medium size molecule > (10 heavy atoms) > >>> > >>> for mol in suppl: > >>> mh = Chem.AddHs(mol, addCoords=True) > >>> > >>> # embedding > >>> start = time.time() > >>> AllChem.EmbedMultipleConfs(mh, numConfs=5000, maxAttempts=100, > pruneRmsThresh=0.5, > >>> randomSeed=1, numThreads=0, > enforceChirality=True, > >>> useExpTorsionAnglePrefs=True, > useBasicKnowledge=True) > >>> cids = [conf.GetId() for conf in mh.GetConformers()] > >>> end = time.time() > >>> print("time eclipsed: ", end - start) > >>> > >>> > >>> The results: > >>> numConfs=1000, time eclipsed: 10 seconds > >>> numConfs=5000, time eclipsed: 66 seconds > >>> numConfs=10000, time eclipsed: 176 seconds > >>> > >>> I need to request a lot more than 10000 conformers per molecule and > have a lot of molecules to process. > >>> I also wish to compute conformer energies and hopefully can do > optimization (both are time consuming). So need to make my code as > efficient as possible. Thank you! > >>> > >>> Best, > >>> Leon > >>> > >>> > >>> _______________________________________________ > >>> Rdkit-discuss mailing list > >>> Rdkit-discuss@lists.sourceforge.net > >>> https://lists.sourceforge.net/lists/listinfo/rdkit-discuss >
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