Dear All,
I was reading through this and can confirm that Yasser is correct, in that GAMD is not a random method but is in fact something that is being more frequently used since 2020.
For example, note this paper where the authors use WT-MetaD coupled to a parallel tempering approach with different values of gamma:
https://pubs.acs.org/doi/10.1021/ct5009087
Note as well the exact same thing here has been done by GAMD and parallel tempering by having consecutive replicas where the potential energy is increasingly elevated:
https://pubs.acs.org/doi/full/10.1021/acs.jctc.4c00501
Similarly, there is a paper here where MetaD methods are used to sample ligand binding:
https://pubs.acs.org/doi/full/10.1021/acs.jcim.6b00772
GAMD being used here to study ligand binding:
https://www.nature.com/articles/s41598-024-58945-4
It is unsurprising that GAMD is now being used to recapitulate a lot of the achievements of MetaD, since restraining potential energy has a similar effect as biasing potential energy as a CV by WT-MetaD until you enter the Well-Tempered ensemble - where the value of gamma affects the fluctuations in potential energy.
I can confirm that GAMD is possible in GROMACS via Plumed but only by using the entire system potential energy as a CV. The idea is to use the system potential energy as the CV for WT-MetaD to generate the well-tempered ensemble for a fixed value of gamma. Both WT-MetaD with system potential energy biased, and GAMD with system potential energy biased, would be more powerful via Plumed if you could select subsets of the system potential energy: e.g. if you could make dihedral angle energies of a protein motif or a ligand the PE term for GAMD. There are then powerful applications for enhancing REST2 by combining it with WT-MetaD or GAMD if you could do this.
See my recommendation here in the Plumed site:
https://groups.google.com/g/plumed-users/c/WLCN5WXkpqg
I agree you will see users switch to AMBER if this is not implemented. I hope I have convinced you that this would be useful to do - you just have to make it such that components or elements of the potential energy function can be selected as an order parameter for biasing, and you would have the implementation fixed for GROMACS. Whether this is done internally or through Plumed is probably something you would all know better.
Kind regards,
Billy