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hesther / espsim

Scoring of shape and ESP similarity with RDKit
MIT License
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New use case - comparison of docking poses #3

Closed Tonylac77 closed 2 years ago

Tonylac77 commented 2 years ago

Hi,

I was interested in using this library to compare docking poses generated using a consensus docking approach. Essentially, I would like to compare the electrostatic field similarity between different poses for a single compound, to use the similarity data to cluster the poses, in a similar fashion that you would do using RMSD values. I am just wondering if it is possible to calculate the field similarity without prior alignment of the two molecules, as the docking poses geometry would need to be conserved. Also the two molecules I would be comparing would be the same compound just in different conformations.

Thanks for any insight you may have,

Tony

hesther commented 2 years ago

Hi @Tonylac77, sorry for the late response, and thank you very much for your question!

In general, it is definitely possible to get shape and ESP similarities while conserving the docking poses, technically. In that case, you would only want to call GetEspSim() and GetShapeSim() where the molecular conformation should be the exact docking pose. Both functions only compute the similarity of the given pose, without any alignment. If you want to keep the geometry, but are ok with rotation and translation of the whole molecule to align, I can give some advice on that too. I can also give some advice on reading in the poses, depending on the format they are saved in.

So, technically it is rather easy and straightforward to get the scores. However, I cannot guarantee how useful the scores are, as I have not tested this use case at all (although we do plan to run some benchmarks in the future). I would be very interested to find out, though, so if you want to give it a try, I would be very grateful if you could report your observations.

If you do not get satisfactory results directly, you might also want to consider using better partial charges than the default ones, e.g. AM1-BCC (which is a separate software that we unfortunately cannot integrate directly, but it is straightforward to run on all poses and read them in with the esp-sim package), I can provide some guidance on that.

hesther commented 2 years ago

Hi, just wanted to add that we included some docking benchmarks and scripts in the new version of the manuscript, just in case you would like to take a look! Also, we now enable machine-learned partial charges, which perform pretty well in our docking benchmarks! Let me know if you have questions!

hesther commented 2 years ago

Hi @Tonylac77, I am closing this issue since I believe it was solved. Feel free to reopen or open a new issue if you have further questions!