2D generalized replica exchange with solute tempering / replica-exchange umbrella sampling (2D gREST/REUS) is a a method to enhance sampling of binding and unbinding events for protein-ligand complexes using replica-exchange molecular dynamics.
2D gREST/REUS enhances sampling of binding and unbinding events by employing replica exchange in two dimensions. One dimension is the ligand-protein distance (REUS dimension) and the other is the temperature (gREST dimension). The change in temperature can be applied over part of a molecule or over energy terms of the system that, if modified, may weaken ligand-protein interactions or enhance the flexibility of residues in the binding site, thus increasing the chances of binding or unbinding events to occur.
For examples of previously performed studies in which 2D generalized replica exchange with solute tempering / replica-exchange umbrella sampling was the primary method used, see the following example cases: