GROMACS version: 2019
GROMACS modification: No
Hi GROMACS users,
I’m new to free energy perturbation and I would greatly appreciate your input. In a nut shell, I wish to alchemically transform an aspartate in a protein’s binding site from de-protonated to protonated sate (the ligand - an ion - does not changes). For this purpose I produced a hybrid protein structure and topology using the pmx server.
First, as this is quite a large system (protein+membrane+solvent), is it legit to equilibrate the system once and then replicate it with the different lambda values in the mdp file, dropping the first x-ns of production for the final analysis?
Second, I would appreciate some input on the following mdp options (a complete mdp file is also attached):
couple-moltype, couple-lambda0 and couple-lambda1: I left these options empty. The gromacs manual implies one cannot use both hybrid topologies and these mdp file options. Is this the case?
couple-intramol = yes: becauese the molecular structure changes (protonation state).
mass_lambdas and bonded-lambdas: as I’m adding a hydrogen atom to my aspartate residue I’m assuming I should set these two options alongside the coul-lambdas and vdw-lambdas. I intend to first decouple the coulombic interactions and then vdw. When should the mass and bonded interactions be decoupled? Parallel to vdw?
sc-coul = no: In equilibrium alchemical free energy calculation only the van der Waals interactions need to be soft-cored. Right?
Any help would be much appreciated!
fep.mdp (4.2 KB)