Native Implementation of REST2


Do I just need to set the protein molecule in couple-moltype and apply lambdas to run a REST2? Along with expanded ensemble options?

Thank you,

I never though of that, but I think that that should actually work! The main disadvantage is performance, as all modified interactions need to go through the free-energy kernels and two PME grid calculations are needed.

You can also use AWH to control lambda.

Note that bonded interactions will not be scaled with this approach.

For other reading this thread, you don’t actually get replica exchange this way, but rather expanded ensemble.

Thank you! Could I also do replica exchange with this approach (rather than expanded ensemble) - just apply the lambda terms to each replica?

Is the only way to apply lambda to the dihedral potentials to apply it to bonded interactions in general?

Also, when the lambda is applied to Lennard-Jones, is the sigma affected or only epsilon?

Thank you,


I don’t recall if GROMACS supported replica exchange on lambda.

You can apply lambda scaling to each bonded term by specifying the force constants for the A and B states. You would need to specify zeros and then the force field force constants for each interaction. That’s extremely tedious, unless you write a script for it.

The Hamiltonians of the A and B states are interpolated linearly, which is exactly what you need for REST2.