Computer Simulations to Explore Membrane Organization and Transport

Over the past half-century, molecular dynamics (MD) simulations have developed from a method for studying the dynamics of pure Lennard-Jones particles to a versatile methodology for studying a broad range of biological systems at the atomic resolution. Recent advances in computer hardware and atomistic simulation algorithms have tremendously increased the timescales accessible to MD simulation by several orders of magnitude from nanosecond timescales to microsecond timescales. The dynamic behaviors of many key biochemical processes, which are hardly observed experimentally, such as protein folding, drug binding, permeation or transport of substrates across cell membrane, could be fully recorded using MD simulations at very fine temporal and spatial resolutions. Membrane proteins account for 20–30% of open reading frames in most genomes and they are targets of over 50% of all modern medicinal drugs. Knowledge of the structure and dynamical behavior of membranes and membrane proteins can greatly enhance the chances for successful pharmaceutical, anesthetic and drug delivery agent developments. However, it remains a big challenge to determine structural information of membrane proteins in experiments compared with soluble proteins. Fortunately, computational approaches, especially MD simulations, can serve as suitable tools to solve this problem and connect the relationship between the membrane protein structure and its physiological functions. In this chapter, we will demonstrate the utility of various theoretical models to investigate membrane proteins.