Problems with RDkit Add Conformers and Optimise Geometry


I’ve been trying to generate low energy conformers of and PMI plots using RDkit and Vernarlis PMI nodes.

The key part of the workflow is ‘RDkit from molecule’ > ‘Salt stripper’ > ‘Add Hs’ > ‘Add Conformers’ > ‘Optimise Geometry’. I’m using default settings for ‘Add conformers’ and MMFF94 for Optimise Geometry. Workflow uploaded.

When I try using molecules representing the vertices (acetylene, benzene and adamantane) I get some very strange (impossible) conformers that all have the same energy. Therefore, when I pick the lowest energy conformer I don’t get the conformers I expect, as depicted in the output PMI plot or by looking at the molecules in a sdf viewer (discovery studio). For the same reason the results aren’t reproducible. More ‘normal’ med chem type molecules seem to work fine, but substituted adamantanes don’t work.

Please could someone let me know where I’m going wrong?

Many thanks
Low energy conformers and PMI.knwf (47.2 KB)

Welcome to the forum @James_Firth

Can you share the input files?

You don’t need the Align to Inertial Principal Axes node.

Which results aren’t reproducible? You haven’t set a random seed for your conformation generation, so the conformations are going to be different every time.

I also don’t see the point of using Optimize Geometry after generating conformers. You already do a cleanup after the calculation anyway.

I also don’t understand your approach to picking the lowest energy conformation.

Thanks for the help, much appreciated.

The adamantane and benzene low energy conformers aren’t reproducible. The optimise geometry function gives all conformers the same energy, including the ones that are chemically impossible.

Input file attached (renamed .sdf to.txt)
PMI Vertices .txt (2.1 KB)