Free energy of mutation - example on an amino acid

User discussions
1

GROMACS version: 2024.4
GROMACS modification: No

Hi everyone, I was thinking of this past post, which is a bug our group spotted, and that was fixed in the latest gromacs 2024.4 version:
Is gmx bar reading dH/dl contibution from masses?

I wonder what this means for the publications on mutation free energy. As far as I know, these parameters are some needed to properly compute it: couple-intramol = yes , vdw-lambdas , coul-lambdas , bonded-lambdas and, finally mass-lambdas series (the latter 4 set to a series different from merely zeros). The first parameter is necessary to consider the contribution of the internal energy of the amino acids (starting one, and mutated) to the total G value of the protein (WT, and mutant). The bonded and mass ones follow accordingly for analogous reasoning (if I am wrong, I am of course here to learn).

Given that the mass variation due to lambda progression from 0 to 1 was not counted in the DG value until the latest gromacs, the kinetics contribution during the mutation was not there, as we indeed verified when reporting. Am I right? Given that many papers have been published on the topic anyway, I think I must be missing something.

Thank you all for your time, and help.

Bests,
Jacopo

2

This is a rather serious issue. But most protocols avoid changing masses, so the impact is likely rather limited. That it only got noticed recently (by you) is proof of this.

Apologies for the very late answer.