Dear Jan,
the reason why your restraint was seemingly not applied is that
MMFFAddTorsionConstraint() expected a range such as (170, 190). I have
just modified the code to make it more robust in this respect and I
submitted a pull request to Greg. Meanwhile, you may get the results you
expect using a (170, 190) degree range.
Please find attached a slightly modified version of your python script;
in particular, I added a call to SetDihedralDeg() before the constrained
minimization, to avoid troubles to the minimizer in case the geometry
generated by EmbedMultipleConfs() has dihedral values very far from the
desired target value.
Thanks for your detailed report which allowed chasing down that weakness
in my code!
Cheers,
Paolo
On 05/10/2014 04:28 PM, Jan Domanski wrote:
Hi there,
Attached is a crystal_ligand.mol2 for the ACE target from DUDE. I'd
like to generate a number of conformers for this ligand. The trick is
it has 2 amide bonds that I'd like to keep planar. As far as I can see
neither MMFF nor UFF will keep those planar by default, at least not
for this input file.
One way around it, is to find all the amide bonds by smarts matching.
From that, find the hydrogen connected to N and add a
DihedralConstraint on the 4 atoms before running the minimization.
That's what conformers.py is attempting to do (basing on one of the
test scripts). However, I still get non-planar amide bonds and I'm
really confused as to why. I can filter them out manually with
GetDihedralDeg().
Thanks for all the help (I'm using up all the rdkit credits this
weekend ;) )
- Jan
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--
==========================================================
Paolo Tosco, Ph.D.
Department of Drug Science and Technology
Via Pietro Giuria, 9 - 10125 Torino (Italy)
Tel: +39 011 670 7680 | Mob: +39 348 5537206
Fax: +39 011 670 7687 | E-mail: paolo.to...@unito.it
http://open3dqsar.org | http://open3dalign.org
==========================================================
import sys
from rdkit import Chem
from rdkit.Chem import AllChem
from rdkit.Chem.rdMolTransforms import GetDihedralDeg, SetDihedralDeg
mol = Chem.MolFromMol2File("crystal_ligand.mol2", removeHs=False)
patt = Chem.MolFromSmarts("[OX1]=CN")
amides = mol.GetSubstructMatches(patt)
constraints = []
for amide in amides:
amide = [mol.GetAtomWithIdx(idx) for idx in amide]
for a in amide: print a.GetSymbol()
carbon = [a for a in amide if a.GetSymbol() == "C"][0]
oxygen = [a for a in amide if a.GetSymbol() == "O"][0]
nitrogen = [a for a in amide if a.GetSymbol() == "N"][0]
# there may be a better way of finding the N-H hydrogen
hydrogens = [ b.GetBeginAtom() for b in nitrogen.GetBonds() if b.GetBeginAtom().GetSymbol() == "H"] + [ b.GetEndAtom() for b in nitrogen.GetBonds() if b.GetEndAtom().GetSymbol() == "H"]
assert(len(hydrogens)==1)
hydrogen = hydrogens[0]
constraint = (hydrogen.GetIdx(), nitrogen.GetIdx(), carbon.GetIdx(), oxygen.GetIdx());
print constraint
constraints.append(constraint)
confIds = AllChem.EmbedMultipleConfs(mol, 200)
prop = AllChem.MMFFGetMoleculeProperties(mol)
for confId in confIds:
conformer = mol.GetConformer(confId)
ff = AllChem.MMFFGetMoleculeForceField(mol, prop, confId=confId)
for c in constraints:
SetDihedralDeg(conformer, c[0], c[1], c[2], c[3], 180)
ff.MMFFAddTorsionConstraint(c[0], c[1], c[2], c[3], False, 170, 190, 1.0e5)
if (ff.Minimize(maxIts=2000)):
print 'confId {0:04d}: insufficient iterations'
for c in constraints:
sys.stdout.write(str(GetDihedralDeg(conformer, c[0], c[1], c[2], c[3])) + '\t')
print
Chem.MolToPDBFile(mol, "conformer_{0:04d}.pdb".format(confId), confId)
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