In my master's thesis I used Hamiltonian replica exchange molecular dynamics (HREMD) to understand the interaction mechanism of two proteins: an epitope of the Plasmodium falciparum AMA1 protein and a monoclonal antibody. In this case, AMA1 has flexible regions, and the enhanced sampling avoids the molecule being trapped in energy barriers with non-representative conformations. Replica exchange was applied to the entire epitope and only to the antigenic site regions of the antibody.
Check the full thesis here: Estudo de Dinâmica Molecular do mecanismo de interação antígeno-anticorpo da proteína AMA1 do Plasmodium falciparum
In the next folders, you will find a step-by-step tutorial to run Molecular Dynamics Simulations with enhanced sampling of a pepitide using PLUMED implemented in GROMACS to perform replica exchanges and solvating the molecule with PACKMOL.
GROMACS: https://www.gromacs.org/
PACKMOL: http://leandro.iqm.unicamp.br/m3g/packmol/home.shtml
m3ggroup: https://github.com/m3g
See this course about this topic: Simulação do enovelamento de proteínas e efeitos de solvente https://github.com/m3g/XEMMSB2021/tree/main