Dissecting Large-Scale Structural Transitions in Membrane Transporters Using Advanced Simulation Technologies

Membrane transporters are integral membrane proteins that act as gatekeepers of the cell, controlling fundamental processes such as recruitment of nutrients and expulsion of waste material. At a basic level, transporters operate using the “alternating access model,” in which transported substances are accessible from only one side of the membrane at a time. This model usually involves large-scale structural changes in the transporter, which often cannot be captured using unbiased, conventional molecular simulation techniques. In this article, we provide an overview of some of the major simulation techniques that have been applied to characterize the structural dynamics and energetics involved in the transition of membrane transporters between their functional states. After briefly introducing each technique, we discuss some of their advantages and limitations and provide some recent examples of their application to membrane transporters.