Absolute Binding Free Energy with pmx

pmx
1

Hi everybody,
I was trying to find some tutorial on pmx to compute ligand absolute binding free energy, however I could only find a lot of tutorial for RELATIVE free energy.
Do you know any practical resources that I can use to understand how to make pmx work for ABFE (especially the new version with python3)?

I am very new to binding energy calculations, so any tutorial/README would be really helpful!

Best,
Andrea

2

Hi Andrea,

please see:

A manual and a working example of the workflows use is available in the workflow_example folder.
The manual also includes the installation instructions for the required version 3 pmx version.

best

Bert

3

Hi Bert,

thank you so much for your quick feedback!

I have been looking into that workflow and I’ve realized that it only works with a scheduler system (and in particular SGE).
Is there a tutorial or some documentation that I could use to run locally outside of any scheduler, or even better without the use of luigi?

Another different problem I have is that I’m working on a system previously prepared with amber and converted to gmx with acpype, hence I would need some manual adjustment with a trial and error phase to set it up correctly, and this luigi workflow looks to me as a “blackbox” on which is hard to have any control unless of course you know how luigi works. Do you have any advice on how to run separately the different parts of pmx for ABFE without the use of luigi ?

Unfortunately on this link pmx I can only find documentation on the relative binding energy… :frowning:

Thank you SO much for your help!

Best,
Andrea

4

Unfortunately this is the only workflow we can provide at the moment. More may follow in the future, so please check back in the future.

Under the hood luigi is running plain pmx and gromacs, so you should be able to see from the output and log files in the different directories what went on, and if/where issues arose. Compare with the tyk2 reference files to see if things worked correctly.

hope that helps!

Bert

1 Like
5

Thank you so much for your suggestion Bert, I’ll try that out.

One more little question though, I have noticed there is another branch on your pmx github for abfe_dev, and I think it is the only one having pmx/src/pmx/AbsoluteDG.py as a module to import. I was able to use that module and I think it is very intuitive since it follows the same logic of the AZtutorial that Vytautas showed in 2021. However I was wondering if it is actually safe to use it or if that module is under development (as the branch name may suggest).

Thanks a lot for your help Bert!

Andrea

6

Yes, this workflow is functional, but use it with caution: it is still under development and may have some rough edges. If you decide to give it a go, I would be interested to hear your feedback to further improve the workflow.

Vytas