I don't have anything to add to the pieces about the alignment (Paolo is
the expert there!), but one comment on the conformation generation: If you
used the background knowledge terms in the embedding, I don't think you
should be getting the really distorted aromatic rings. Since in this case
that does happen, for at least some conformations, I suspect there may be
something wrong in the code.
I'll take a look at that (and ask Sereina too).
Best,
-greg
On Tue, Jun 21, 2016 at 10:30 PM, Paolo Tosco <paolo.to...@unito.it> wrote:
> Dear Tim,
>
> the Align() method returns an RMSD value, which however is computed only
> on a limited number of atom pairs, namely those that the algorithm was able
> to match between the two molecules, so a low value is not particularly
> informative of the overall goodness of the alignment, as it only indicates
> that the matched atoms were matched nicely, but there might only be a few
> of those in the core, while side chains are scattered all over.
> The Score() method instead returns the O3AScore for the alignment, which
> is a better way to assess the quality of the superimposition.
>
> The other problem in your script is that the i index is incremented before
> recording it in the lowest/highest variables, so the confIds are shifted by
> 1, as the conformation index in the RDKit is 0-based.
>
> I also noticed that without minimizing the conformations the aromatic
> rings look quite distorted, so I added a MMFF minimization, and I increased
> the number of generated conformations and the pruneRmsThreshold. Setting to
> False the experimental torsion angle preferences and basic knowledge about
> rings seems to yield a larger variety of geometries which helps reproducing
> this quite peculiar x-ray geometry which is probably not so commonly found.
> Please find the modified script below.
>
> Hope this helps, kind regards
> Paolo
>
>
> #!/usr/bin/env python
>
>
> from rdkit import Chem, RDConfig
> from rdkit.Chem import AllChem, rdMolAlign
>
> ref = Chem.MolFromSmiles('NC(=[NH2+])c1ccc(C[C@
> @H](NC(=O)CNS(=O)(=O)c2ccc3ccccc3c2)C(=O)N2CCCCC2)cc1')
> mol1 =
> Chem.MolFromPDBFile(RDConfig.RDBaseDir+'/rdkit/Chem/test_data/1DWD_ligand.pdb')
> mol1 = AllChem.AssignBondOrdersFromTemplate(ref, mol1)
> mol2 =
> Chem.MolFromPDBFile(RDConfig.RDBaseDir+'/rdkit/Chem/test_data/1PPC_ligand.pdb')
> mol2 = AllChem.AssignBondOrdersFromTemplate(ref, mol2)
>
> pyO3A = rdMolAlign.GetO3A(mol1, mol2)
> rmsd = pyO3A.Align()
> score = pyO3A.Score()
> print "Orig",score
> Chem.MolToMolFile(mol1, "orig.mol")
>
> cids = AllChem.EmbedMultipleConfs(mol1, numConfs=250, maxAttempts=100,
> pruneRmsThresh=0.5, useExpTorsionAnglePrefs=False,
> useBasicKnowledge=False)
> AllChem.MMFFOptimizeMoleculeConfs(mol1, mmffVariant='MMFF94s')
> pyO3As = rdMolAlign.GetO3AForProbeConfs(mol1, mol2, numThreads=0)
> i = 0
> lowest = 999999999.9
> highest = 0.0
> for pyO3A in pyO3As:
> rmsd = pyO3A.Align()
> score = pyO3A.Score()
> if score < lowest:
> lowest = score
> lowestConfId = i
> if score > highest:
> highest = score
> highestConfId = i
> i +=1
>
> print "Lowest:", lowest, lowestConfId
> print "Highest:", highest, highestConfId
>
> Chem.MolToMolFile(mol1, "lowest.mol", confId=lowestConfId)
> Chem.MolToMolFile(mol1, "highest.mol", confId=highestConfId)
>
>
> On 06/21/16 15:41, Tim Dudgeon wrote:
>
> Hi All,
>
> I'm trying to get to grips with using Open3D Align in RDKit, but hitting
> problems.
>
> My approach is to generate random conformers of the probe molecule and
> align it to the reference molecule. My example is cobbled together from
> the examples in the cookbook.
>
> from rdkit import Chem, RDConfig
> from rdkit.Chem import AllChem, rdMolAlign
>
> ref = Chem.MolFromSmiles('NC(=[NH2+])c1ccc(C[C@
> @H](NC(=O)CNS(=O)(=O)c2ccc3ccccc3c2)C(=O)N2CCCCC2)cc1')
> mol1 =
> Chem.MolFromPDBFile(RDConfig.RDBaseDir+'/rdkit/Chem/test_data/1DWD_ligand.pdb')
> mol1 = AllChem.AssignBondOrdersFromTemplate(ref, mol1)
> mol2 =
> Chem.MolFromPDBFile(RDConfig.RDBaseDir+'/rdkit/Chem/test_data/1PPC_ligand.pdb')
> mol2 = AllChem.AssignBondOrdersFromTemplate(ref, mol2)
>
> pyO3A = rdMolAlign.GetO3A(mol1, mol2)
> score = pyO3A.Align()
> print "Orig",score
> Chem.MolToMolFile(mol1, "orig.mol")
>
> cids = AllChem.EmbedMultipleConfs(mol1, numConfs=100, maxAttempts=100,
> pruneRmsThresh=0.1, useExpTorsionAnglePrefs=True, useBasicKnowledge=True)
>
> pyO3As = rdMolAlign.GetO3AForProbeConfs(mol1, mol2, numThreads=0)
> i = 0
> lowest = 999999999.9
> highest = 0.0
> for pyO3A in pyO3As:
> i +=1
> score = pyO3A.Align()
> if score < lowest:
> lowest = score
> lowestConfId = i
> if score > highest:
> highest = score
> highestConfId = i
>
> print "Lowest:", lowest, lowestConfId
> print "Highest:", highest, highestConfId
>
> Chem.MolToMolFile(mol1, "lowest.mol", confId=lowestConfId)
> Chem.MolToMolFile(mol1, "highest.mol", confId=highestConfId)
>
> What I'm finding is that the alignments with the lowest and highest O3A
> scores are much worse alignments (visually) than the original structure
> (the structure from 1DWD). Typical scores are:
>
> Original 1DWD structure: 0.38
> Lowest scoring conformer: 0.186
> Highest scoring conformer: 0.78
>
> Now I'm assuming that lower O3A align scores are better (though that's not
> specifically stated), so as my lowest score is lower than the original
> alignment I would have expected it to be a better alignment, but its
> clearly much worse. And if I'm wrong and higher scores are better then the
> same applies.
>
> Clearly I've not understood something correctly!
>
> Tim
>
>
> ------------------------------------------------------------------------------
> Attend Shape: An AT&T Tech Expo July 15-16. Meet us at AT&T Park in San
> Francisco, CA to explore cutting-edge tech and listen to tech luminaries
> present their vision of the future. This family event has something for
> everyone, including kids. Get more information and register
> today.http://sdm.link/attshape
>
>
>
> _______________________________________________
> Rdkit-discuss mailing
> listRdkit-discuss@lists.sourceforge.nethttps://lists.sourceforge.net/lists/listinfo/rdkit-discuss
>
>
>
>
> ------------------------------------------------------------------------------
> Attend Shape: An AT&T Tech Expo July 15-16. Meet us at AT&T Park in San
> Francisco, CA to explore cutting-edge tech and listen to tech luminaries
> present their vision of the future. This family event has something for
> everyone, including kids. Get more information and register today.
> http://sdm.link/attshape
> _______________________________________________
> Rdkit-discuss mailing list
> Rdkit-discuss@lists.sourceforge.net
> https://lists.sourceforge.net/lists/listinfo/rdkit-discuss
>
>
------------------------------------------------------------------------------
Attend Shape: An AT&T Tech Expo July 15-16. Meet us at AT&T Park in San
Francisco, CA to explore cutting-edge tech and listen to tech luminaries
present their vision of the future. This family event has something for
everyone, including kids. Get more information and register today.
http://sdm.link/attshape
_______________________________________________
Rdkit-discuss mailing list
Rdkit-discuss@lists.sourceforge.net
https://lists.sourceforge.net/lists/listinfo/rdkit-discuss
