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
<mailto: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 list
Rdkit-discuss@lists.sourceforge.net
<mailto: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
<mailto: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
<mailto:Rdkit-discuss@lists.sourceforge.net>
https://lists.sourceforge.net/lists/listinfo/rdkit-discuss
