Free Energy, Rates, and Mechanism of Transmembrane Dimerization in Lipid Bilayers from Dynamically Unbiased Molecular Dynamics Simulations.

ABSTRACT: The assembly of proteins in membranes plays a key role in many crucial cellular pathways. Despite their importance, characterizing transmembrane assembly remains challenging for experiments and simulations. Equilibrium molecular dynamics simulations do not cover the time scales required to sample the typical transmembrane assembly. Hence, most studies rely on enhanced sampling schemes that steer the dynamics of transmembrane proteins along a collective variable that should encode all slow degrees of freedom. However, given the complexity of the condensed-phase lipid environment, this is far from trivial, with the consequence that free energy profiles of dimerization can be poorly converged. Here, we introduce an alternative approach, which relies only on simulating short, dynamically unbia

SUBMITTER: Jackel E 

PROVIDER: S-EPMC11808646 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature