Applications and Energetics of a Novel Atomistic Membrane Representation

Joshua Vermaas, University of Illinois at Urbana-Champaign

Cellular membranes are a dynamic environment in which membrane lipids play an active role in regulating membrane and peripheral proteins. Thus there is considerable interest in understanding the mechanistic details of the interactions that take place between the membrane and its associated proteins. The unparalleled spatial and temporal resolution offered by molecular dynamics (MD) simulations makes it an ideal tool for studying the mechanics of the membrane dynamical organization and of the protein-membrane interactions at the atomistic level of detail.

In the initial stages of the membrane insertion events, lipid dynamics plays an important role. The hydrophilic head groups interact with and must accommodate the inserting species as it embeds into the bilayer. This process is limited by slow lipid exchange and thus is challenging to model with conventional atomistic MD. Through the development of a novel membrane representation with faster lipid exchange, we capture spontaneous insertion events more rapidly than in MD studies with a conventional bilayer.

The way the Highly Mobile Membrane Mimetic (HMMM) membrane representation accelerates insertion is through the replacement of portions of the membrane acyl chains with an organic solvent, while leaving lipid head groups intact. By changing the composition of the membrane, we have achieved faster kinetics, but have we appreciably changed the equilibrium state itself? To answer this question, we calculated the free energies of side chain analogues insertion into the HMMM bilayer. The weighted histogram analysis method was used with the umbrella sampling data. The insertion free energy profiles compare favorably with those reported for conventional bilayers in the head group region. The accuracy of the interfacial interactions adds validity to the observations of spontaneous lipid insertion into the HMMM membranes.

Abstract Author(s): Joshua Vermaas, Taras V. Pogorelov and Emad Tajkhorshid