Dear community,
I am having problems using the constrained embed function. I want to generate
3D coordinates for structural variants of a macrocycle, whereas the cycle
backbone itself is stable and therefore my template. I provide the stable
backbone as an .sdf and the structural variants as SMILES to the function. I
have different errors, depending on the particular structure.
On the one hand I observe a Value Error:
ValueError Traceback (most recent call last)
<ipython-input-23-69147410d36f> in <module>()
----> 1 out = AllChem.ConstrainedEmbed(mc, bb, useTethers=True, randomseed=1,
getForceField=GetFF, useRandomCoords=True)
C:\ProgramData\Anaconda3\lib\site-packages\rdkit\Chem\AllChem.py in
ConstrainedEmbed(mol, core, useTethers, coreConfId, randomseed, getForceField,
**kwargs)
283 ci = EmbedMolecule(mol, coordMap=coordMap, randomSeed=randomseed,
**kwargs)
284 if ci < 0:
--> 285 raise ValueError('Could not embed molecule.')
286
287 algMap = [(j, i) for i, j in enumerate(match)]
ValueError: Could not embed molecule.
However, based on an old discussion entry with an apparent similar problem
(https://sourceforge.net/p/rdkit/mailman/message/32082674/) I tried the very
same preliminary solution (setting ignoreSmoothingFailures=True) which works
fine. The post is from 2014, therefore I wonder if there is a better solution
by now?
On the other hand, while applying the fix above, i observe a different error
with specific compounds of my set of variants:
AttributeError Traceback (most recent call last)
<ipython-input-59-c91b6839ef04> in <module>()
----> 1 out = AllChem.ConstrainedEmbed(mc, bb, useTethers=True, randomseed=-1,
getForceField=GetFF,ignoreSmoothingFailures=True, useRandomCoords=True)
C:\ProgramData\Anaconda3\lib\site-packages\rdkit\Chem\AllChem.py in
ConstrainedEmbed(mol, core, useTethers, coreConfId, randomseed, getForceField,
**kwargs)
310 for i in range(core.GetNumAtoms()):
311 p = conf.GetAtomPosition(i)
--> 312 pIdx = ff.AddExtraPoint(p.x, p.y, p.z, fixed=True) - 1
313 ff.AddDistanceConstraint(pIdx, match[i], 0, 0, 100.)
314 ff.Initialize()
AttributeError: 'NoneType' object has no attribute 'AddExtraPoint'
What differs the compounds, which show this error, from the rest, is a selenium
linked phenylgroup. In fact, replacing the selenium by a carbon fixes this
error. Interestingly, the function still outputs a structure, which is however
chemically wrong (non-planar rings). Not applying the fix from 2014 also gives
the "ValueError: Could not embed molecule."- error.
I attached the .sdf of the backbone and two canonical smiles.
backbone 3d coordinates:
G:\MC_gen_test\test2_bb.pdb
OpenBabel07191818263D
25 25 0 0 0 0 0 0 0 0999 V2000
81,0000 22,0000 24,0000 C 0 0 0 0 0 0 0 0 0 0 0 0
83,0000 22,0000 23,0000 N 0 0 0 0 0 0 0 0 0 0 0 0
81,0000 23,0000 24,0000 C 0 0 0 0 0 0 0 0 0 0 0 0
81,0000 24,0000 24,0000 N 0 0 0 0 0 0 0 0 0 0 0 0
81,0000 26,0000 24,0000 C 0 0 0 0 0 0 0 0 0 0 0 0
82,0000 26,0000 26,0000 C 0 0 0 0 0 0 0 0 0 0 0 0
83,0000 25,0000 26,0000 N 0 0 0 0 0 0 0 0 0 0 0 0
83,0000 25,0000 28,0000 C 0 0 0 0 0 0 0 0 0 0 0 0
84,0000 26,0000 28,0000 C 0 0 0 0 0 0 0 0 0 0 0 0
85,0000 26,0000 27,0000 N 0 0 0 0 0 0 0 0 0 0 0 0
86,0000 27,0000 27,0000 C 0 0 0 0 0 0 0 0 0 0 0 0
86,0000 28,0000 25,0000 C 0 0 0 0 0 0 0 0 0 0 0 0
86,0000 27,0000 24,0000 C 0 0 0 0 0 0 0 0 0 0 0 0
87,0000 27,0000 23,0000 N 0 0 0 0 0 0 0 0 0 0 0 0
88,0000 26,0000 22,0000 C 0 0 0 0 0 0 0 0 0 0 0 0
89,0000 25,0000 23,0000 C 0 0 0 0 0 0 0 0 0 0 0 0
90,0000 26,0000 24,0000 N 0 0 0 0 0 0 0 0 0 0 0 0
91,0000 25,0000 24,0000 C 0 0 0 0 0 0 0 0 0 0 0 0
91,0000 24,0000 25,0000 C 0 0 0 0 0 0 0 0 0 0 0 0
90,0000 23,0000 25,0000 C 0 0 0 0 0 0 0 0 0 0 0 0
84,0000 22,0000 24,0000 C 0 0 0 0 0 0 0 0 0 0 0 0
85,0000 22,0000 23,0000 C 0 0 0 0 0 0 0 0 0 0 0 0
86,0000 23,0000 24,0000 C 0 0 0 0 0 0 0 0 0 0 0 0
87,0000 22,0000 24,0000 C 0 0 0 0 0 0 0 0 0 0 0 0
88,0000 23,0000 25,0000 N 0 0 0 0 0 0 0 0 0 0 0 0
1 2 1 0 0 0 0
1 3 1 0 0 0 0
2 21 1 0 0 0 0
3 4 1 0 0 0 0
4 5 1 0 0 0 0
5 6 1 0 0 0 0
6 7 1 0 0 0 0
7 8 1 0 0 0 0
8 9 1 0 0 0 0
9 10 1 0 0 0 0
10 11 1 0 0 0 0
11 12 1 0 0 0 0
12 13 1 0 0 0 0
13 14 1 0 0 0 0
14 15 1 0 0 0 0
15 16 1 0 0 0 0
16 17 1 0 0 0 0
17 18 1 0 0 0 0
18 19 1 0 0 0 0
19 20 1 0 0 0 0
20 25 1 0 0 0 0
21 22 1 0 0 0 0
22 23 1 0 0 0 0
23 24 1 0 0 0 0
24 25 1 0 0 0 0
M END
$$$$
A smiles which works with the 2014 "ignoreSmoothingFailures=True"-fix, but not
without:
C=C1C(=O)NC(C)C(=O)NC(CC(C)C)C(=O)NC(C(=O)O)C(C)C(=O)NC(CCCN=C(N)N)C(=O)NC(C=CC(C)=CC(C)C(Cc2ccccc2)OC)C(C)C(=O)NC(C(=O)O)CCC(=O)N1C
A smiles with a selenium, which additionally gives an Attribute Error:
C=C1C(=O)NC(C)C(=O)NC(CC(C)C)C(=O)NC(C(=O)O)C(C)C(=O)NC(Cc2ccccc2)C(=O)NC(C=CC(C)=CC(C)C(Cc2ccccc2)OC)C(C)C(=O)NC(C(=O)O)CCC(=O)N1[Se]c1ccccc1
Any advice is appreciated!
Best wishes,
Jahn Nitschke
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