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UCL-CCS / TIES

Topology Superimposition based on joint graph traversal
MIT License
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Examples of Protein residue mutation? #316

Open aminsagar opened 1 year ago

aminsagar commented 1 year ago

Dear TIES developers,

I would like to setup some FEP simulations for a protein-peptide system where I mutate a residue of the peptide. This seems similar to TIES-PM (https://doi.org/10.1021/acs.jctc.8b01118), except the mutation is in the peptide ligand. The examples only include small molecule ligand modifications. Are point mutations of proteins also possible with this version of TIES? It would be really great if you can share a small example of how to do this.

Best, Amin.

adw62 commented 1 year ago

Hi Amin,

Sorry for the slow reply. We have a separate workflow for proteins, since they are larger it can be harder to compute the hybrid structure. We would be happy to share with you the scripts needed for protein mutations if you would like?

We have only tested the code in this GitHub repo with small drug like molecules but depending on the size of the peptide it could work. Do you have any details you could share about the system size or maybe an example system we could help you get working?

Cheers, Alex

aminsagar commented 1 year ago

Thanks a lot for your response and sorry for my delayed reply. The system I am trying to study is around 300 residues long protein and a 14 residue long peptide. I would like to mutate a single residue of the peptide at a time to estimate the change in affinity. I would be really thankful if you can share the scripts. I can try them on my system and report back the results.

Thanks, Amin.

adw62 commented 1 year ago

Sure no problem, my colleague @apbhati1 can send through the scripts shortly.

A 14 residue long peptide might also be small enough to use the code in this repo. @bieniekmateusz could you please comment on if TIES 20 will work with a 14 residue long peptide?

Cheers, Alex

bieniekmateusz commented 1 year ago

14 residue might be just about the limit of what our superimposition can do, but I would expect it to take around 30 minutes. Thanks, Mat