[Rdkit-discuss] 2D Coordinates for RNA

[<tho...@bo...>]

Dear all,

I am working with peptides and RNA and want to convert sequences into 2D molecules.
As we use non-natural and proprietary monomers, I cannot apply the ususal workflows like MolFromHELM,
but have developed my own python code to build the macromolecules from their building blocks (basically
using Chem.CombineMols and then rdDepictor.Compute2DCoords,
see https://github.com/Boehringer-Ingelheim/pyPept/blob/master/src/pyPept/molecule.py).

While this works fine for even large peptides (>40 monomers), when doing the same for RNA I run into a problem:
after a certain size (about 12 or 13 nucleotides), the 2D embedding returns all coordinates as zeroes and all stereoinformation
is lost.

I tried the same using MolFromHELM, and there I do not see the same issue, I get valid 2D coordinates up to hundreds of nucleotides
(yes, other than what the documentation says, RNA and DNA work, too!).
Only if I first generate the molecule and then pass it through either rdCoordGen.AddCoords or Chem.rdDepictor.Compute2DCoords
I end up with coordinates as zero. So I suppose MolFromHELM knows sth about the general structure of the building blocks and uses that information,
whereas the all-purpose embedders cannot take that into account and subsequently fail. But then again, this MolFromHELM is not an option as I need non-natural
monomers (unless there is a way to teach rdkit about non-canonical monomers, but I haven't found anything on it).

Here is the relevant code snippet:

from rdkit import Chem
from rdkit.Chem import rdCoordGen

n_nucleotides = 20

polyA = ['R(A)P'] * n_nucleotides
polyA = '.'.join(polyA)
helm = f'RNA1{{{polyA}}}$$$$V2.0'

romol = Chem.MolFromHELM(helm)
#rdCoordGen.AddCoords(romol)

mb = Chem.MolToMolBlock(romol)

print(mb[1:300])

Now everything looks fine, but as soon as I uncomment the rdCoordGen line, the coordinates are zero.

Any ideas, suggestions what I could do?

Thanks,
Th.


Thomas Fox
NCE

Boehringer Ingelheim Pharma GmbH & Co. KG
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