Upcoming Event: Molecular BioPhysics Seminar Series

Understanding the thermodynamics of phase separation in lipid membranes using molecular simulations

Alan Grossfield, University of Rochester Medical Center

Abstract

Cellular membranes are exceptionally chemically diverse, containing dozens of lipid species, many of which do not mix easily. The “lipid raft” hypothesis posits the formation of ordered domains floating in a sea of disordered lipids. The resulting lipid domains often have functional roles. However, the thermodynamics of lipid phase separation and their resulting mechanistic effects on cell function and dysfunction are poorly understood. Model systems with simpler compositions can recapitulate this behavior, and are widely used to study this phenomenon. Despite these simplifications, the timescale and length scales of domain formation a challenge for molecular dynamics (MD) simulations. Thus, most MD studies focus on spontaneous lipid phase separation, measuring the sign but not the amplitude of the free energy change upon separation. We have developed a new method, based around the weighted ensemble sampling algorithm and a clustering-based collective variable, that allows us to compute the free energy of phase separation directly from simulations.  This technique will be a useful tool to help connect the thermodynamics of phase separation with the mechanistic insights already available from molecular dynamics simulations.

Biography

Alan Grossfield's research interests revolve around the use of computer modeling to understand the structure and thermodynamics of biological molecules. In particular, he is most interested in understanding the biology and physics of lipid-protein interactions. These interactions underlie a fantastic array of biological processes, including cell-signaling by GPCRs and some immune reactions, specifically the action of antimicrobial peptides.