Analysis of Lipid Order States and Domains in Lipid Bilayer Simulations

We propose a general procedure to analyze lipid order states and domains in lipid bilayer simulations using surface areas and hydrophobic thicknesses of lipids. In our approach, the observable order states of individual lipids are inferred by a hidden Markov model analysis of their time series and by considering the deformation of a lipid in different packing environments. The assigned lipid order states are mapped onto the Voronoi tessellation of lipids, from which the ordered and disordered lipids are robustly clustered by the Getis-Ord local spatial autocorrelation statistics. The usefulness of this method is illustrated by its application to the quinary mixed bilayers consisting of cholesterol (Chol), 1,2-dimyristoyl- sn-glycero-3-phosphocholine (DMPC), 1,2-dimyristoyl- sn-glycero-3-phosphoethanolamine (DMPE), 1-palmitoyl-2-oleoyl- sn-glycero-3-phosphocholine (POPC), and 1-palmitoyl-2-oleoyl- sn-glycero-3-phosphoethanolamine (POPE), where any phospholipid type does not show strong preference over the other types to be enriched in lipid domains. The independent order state analysis for each lipid type allows straightforward applications of our method to arbitrarily complex bilayer simulations.