Density-biased sampling: A robust computational method for studying pore formation in membranes

Abstract

A new reaction coordinate to bias molecular dynamics simulation is described that allows enhanced sampling of density-driven processes, such as mixing and demixing two different molecular species. The methodology is validated by comparing the theoretical entropy of demixing two ideal gas species and then applied to induce deformation and pore formation in phospholipid membranes within an umbrella sampling framework. Comparison with previous biased simulations of membrane pore formation suggests overall quantitative agreement, but the density-based biasing potential results in a different, more realistic transition pathway than that in previous studies.