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Valdes-Tresanco-MS / gmx_MMPBSA

gmx_MMPBSA is a new tool based on AMBER's MMPBSA.py aiming to perform end-state free energy calculations with GROMACS files.
https://valdes-tresanco-ms.github.io/gmx_MMPBSA/
GNU General Public License v3.0
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[Question]: Discrepancy in Binding Free Energy Results between GMX_MMPBSA v1.6.1 and v1.4.3 #402

Closed aqrzsy closed 1 year ago

aqrzsy commented 1 year ago

My Question is...

Hello, I've encountered a significant discrepancy in the results of binding free energy calculations when using two different versions of gmx_mmpbsa. Version Details: Using version 1.6.1, the computed binding free energy was over 512 kcal/mol. When I downgraded to version 1.4.3 and used the exact same input files, the result was -13kcal/mol, which is more in line with what I expected. Question: Is there any specific parameter or settings change between the two versions that could explain such a drastic difference? Are there any recommended settings or parameters that should be adjusted when using version 1.6.1? Any insight into this discrepancy would be highly appreciated. Thank you!

marioernestovaldes commented 1 year ago

can you send us the files you are using with the results? I wouldn't expect such a difference considering the core of the program hasn't changed

aqrzsy commented 1 year ago

Here are my files and results. I'm sorry, the md.xtc file is too large to upload. files and results.zip

marioernestovaldes commented 1 year ago

It seems you are using a different number of frames in the calculations... please, make sure you are using exactly the same frames in both calculations, and let us know if the issue persists

aqrzsy commented 1 year ago

I'm sorry, but this is the result I obtained using version 1.4.3, recalculating with the same number of frames as in version 1.6.1. The difference is still significant. 1.4.3FINAL_RESULTS_MMPBSA.dat.zip

marioernestovaldes commented 1 year ago

could you please share the trajectory file, thus we can perform the analysis?

Valdes-Tresanco-MS commented 1 year ago

The main change from version 1.4.x to 1.6.x is the calculation of the non-polar component of the solvation. Please compare (and attach) the _GMXMMPBSA_info files of both versions to corroborate that you are using the same parameters.