Thermodynamics and Free Energy Landscape of BAR-Domain Dimerization from Molecular Simulations.

ABSTRACT: Proteins with BAR domains function to bind to and remodel biological membranes, where the dimerization of BAR domains is a key step in this function. These domains can dimerize in solution or after localizing to the membrane surface. Here, we characterize the binding thermodynamics of homodimerization between the LSP1 BAR domain proteins in solution, using molecular dynamics (MD) simulations. By combining the MARTINI coarse-grained protein models with enhanced sampling through metadynamics, we construct a two-dimensional free energy surface quantifying the bound versus unbound ensembles as a function of two distance variables. With this methodology, our simulations can simultaneously characterize the structures and relative stabilities of a range of sampled dimers, portraying a heterogeneo

SUBMITTER: Jhaveri A 

PROVIDER: S-EPMC8224822 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature