Analysis of the Area Per Lipid in Protein-Membrane Systems

Abstract

Molecular dynamics (MD) simulation is a powerful research tool to investigate structural and dynamical properties of biological membranes and membrane proteins. The lipid structures of simple membrane systems in recent MD simulations are in good agreement with those obtained by experiments. However, for protein-membrane systems the complexity of protein-lipid interactions makes investigation of lipid structure more difficult. Although the area per lipid is one of the important structural properties of membranes, the area in protein-membrane systems cannot be calculated easily by conventional approaches like Voronoi tessellation method. Here, we developed a new method, based on a combination of the two-dimensional Voronoi tessellation and Monte Carlo integration methods. Monte Carlo integration enables us to estimate the cross-sectional area of arbitrary-shaped target molecules. We applied the method to all-atom MD trajectories of the sarcoplasmic reticulum Ca2+-pump and the SecY protein-conducting channel. The calculated lipid surface area was in agreement with experimental values and consistent with other structural parameters of lipid bilayers. We also observed a response of lipid bilayers to the conformational transition of SecY. We believe that our method is useful to analyze time courses of protein-lipid interactions in MD simulations of membrane proteins.