Accurate coarse-grain modeling of biomembranes

COMP 61

Julien Michel, mail@julienmichel.net1, Mario Orsi1, Wendy Sanderson, wsanders@prdbe.jnj.com2, and Jonathan W Essex, jwe1@soton.ac.uk1. (1) School of Chemistry, University of Southampton, Highfield, Southampton, SO17 1BJ, United Kingdom, (2) Molecular Informatics, Johnson & Johnson Pharmaceutical Research & Development, Turnhoutseweg 30, Beerse, 2340, Belgium
An efficient and accurate model of a fluid phase DMPC lipid bilayer is presented. The lipid molecules are represented by a combination of Lennard Jones and anisotropic Gay Berne potentials. Unlike many existing coarse-grain models, electrostatic interactions are fully retained through inclusion of dipoles and charges. Water is modeled by the soft sticky dipole potential. The methodology is orders of magnitude more efficient than atomistic simulations. Starting from a random solution, lipids spontaneously self-assemble into a bilayer that reproduces quantitatively all major experimentally-determined physical properties of membranes. Furthermore, the potentials employed are compatible with all atom force fields. We show that interactions between atomistic and coarse-grain particles can be tuned until water-octane partition coefficients of small molecules are predicted with good accuracy. We discuss applications to drug permeability studies and how the present approach can be extended to model other components of biological membranes.