Exploring atomic resolution physiology on a femtosecond to millisecond timescale using molecular dynamics simulations

Abstract

Discovering the functional mechanisms of biological systems frequently requires information that challenges the spatial and temporal resolution limits of current experimental techniques. Recent dramatic methodological advances have made all-atom molecular dynamics (MD) simulations an ever more useful partner to experi- ment because MD simulations capture the atomic resolution behavior of biological systems on timescales spanning 12 orders of magnitude, covering a spatiotemporal domain where experimental characterization is often difficult if not impossible. We present here our perspective on the mechanistic insights that a scientist —in particular, a membrane protein physiologist— might garner by complementing experiments with atomistic MD simulations. Drawing on case studies from our work, we illustrate the diversity of membrane proteins amenable to study by MD and the types of discoveries one can make through simulation. We discuss the strengths and limitations of MD as a tool for physiologists, and we speculate on advances that such simulations may enable in the coming years.