Atomistic and coarse-grained simulations of membrane proteins: A practical guide.

Abstract

Membrane proteins are amphipathic macromolecules whose exposed hydrophobic surfaces promote interactions with lipid membranes. Membrane proteins are remarkably diverse in terms of chemical composition and correspondingly, their biological functions and general biophysical behavior. Conventional experimental techniques provide an approach to study specific properties of membrane proteins e.g. their surface features, the nature and abundance of stabilizing intramolecular forces, preferred bilayer orientation, and the characteristics of their annular lipid shells. Molecular modeling software-and in particular, the suite of molecular dynamics algorithms-enables a more comprehensive exploration of dynamic membrane protein behavior. Molecular dynamics methods enable users to produce stepwise trajectories of proteins on arbitrary spatiotemporal scales that enable the easy identification of dynamic interactions that are beyond the scope of conventional analytical techniques. This article explains the molecular dynamics theoretical framework and popular step-by-step approaches for simulating membrane proteins in planar, and to a lesser extent, nonplanar lipid geometries. We detail popular procedures and computational tools that produce well-packed configurations of lipids and proteins and additionally, the efficient molecular dynamics simulation algorithms that reproduce their dynamic interactions.