GROMACS version: All
GROMACS modification: No
I am starting FEP calculations and I am a little bit confused with the restraints. I want to compute the absolute binding free energy of a very small ligand to a target protein, and I need to add restraints otherwise when both coulombic and vdw interactions are set to zero the ligand wanders. I will probably use 2 or 3 harmonic potentials. What is the recommanded strategy with Gromacs: a section “[ intermolecular_interactions ]” in the topology file, or using the pull code in the .mdp file?
Then, I was thinking using restraint-lambdas in the .mdp file, but I see in this tutorial Absolute Binding Free Energy - Gromacs 2016 - AlchemistryWiki that they are using bonded-lambdas which confuses me. Maybe they are using bonded-lambdas because they are using intermolecular_interactions?
Finally, I don’t understand how Gromacs can be aware of which restraints to add/remove: if I use the pull code to keep my ligand in place, but also to add another restraint far from the binding site, when the restraints are added with restraint-lambdas how Gromacs knows which one to add? Is it because in
he .mdp I say the I want do apply FEP to the molecule LIG and then Gromacs checks which coordinates from the pull code involve atoms from LIG? (and the same applies when intermolecular_interactions are used).
Thank you for your help