Convergence and Sampling in Determining Free Energy Landscapes for Membrane Protein Association.

ABSTRACT: Potential of mean force (PMF) calculations are used to characterize the free energy landscape of protein-lipid and protein-protein association within membranes. Coarse-grained simulations allow binding free energies to be determined with reasonable statistical error. This accuracy relies on defining a good collective variable to describe the binding and unbinding transitions, and upon criteria for assessing the convergence of the simulation toward representative equilibrium sampling. As examples, we calculate protein-lipid binding PMFs for ANT/cardiolipin and Kir2.2/PIP₂, using umbrella sampling on a distance coordinate. These highlight the importance of replica exchange between windows for convergence. The use of two independent sets of simulations, initiated from bound and unb

SUBMITTER: Domanski J 

PROVIDER: S-EPMC5402295 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature