Simultaneous Construction of Free Energy Surfaces via Multisite λ Dynamics and Umbrella Sampling.

ABSTRACT: Umbrella sampling (US) is a cornerstone enhanced sampling technique that constructs potentials of mean force (PMF) by biasing a system of interest along a set of collective variables (CV). With a good choice of CVs, one can uncover the free energy landscapes governing a plethora of biological processes such as protein-ligand (un)binding, protein (un)folding, and enzyme catalysis. However, multiple sets of umbrella simulations have to be run when one is interested in exploring how the free energy landscape of a particular process varies with chemical space, such as the effects of different mutations on the (un)folding landscape or how different ligands (un)bind to the same protein. We propose an enhanced sampling framework called MSλD + US that couples umbrella sampling with multisite λ dyn

SUBMITTER: Lai TT 

PROVIDER: S-EPMC12413840 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature