Elucidating membrane protein function through long-timescale molecular dynamics simulation

Recent advances in algorithms, software, and hardware for molecular dynamics (MD) simulations have brought previously inaccessible simulation timescales within reach, allowing the use of MD simulation to address a substantially broader set of questions regarding protein function. MD has proved particularly useful in elucidating the functional mechanisms of membrane proteins, whose dynamics are especially difficult to characterize experimentally. Here, we illustrate the utility of state-of-the-art high-performance MD simulations in the study of membrane proteins, using as examples a G-protein-coupled receptor, an aquaporin, and an antiporter. In each case, we used MD either to deduce an atomic-level mechanism for protein function or to reconcile apparent discrepancies among recent experimental observations.