A Continuum Model for Simulation of Large Biological Lipid Membranes

Abstract

Joint Design of Advanced Computing Solutions for Cancer (JDACS4C) - Pilot 2 Team. Presented by: Timothy S. Carpenter. Membrane proteins have important cellular roles and comprise the vast majority of drug targets. Membrane proteins interact strongly with the lipids, and protein function can be affected by local lipid compositions. To properly explore this relationship requires a bilayer that is not only of sufficient size to contain relevant compositional fluctuations, but is also run for enough time for proteins to react to both local lipid compositions and other nearby proteins. The appropriate length- and time-scales are at least microns and milliseconds. Concurrently, the mechanisms of interaction between lipids and proteins are defined by molecular structure at the sub-nanometer scale, and are typically explored by molecular dynamics simulations limited to just microseconds of time evolution.Within the JDACS4C Pilot 2 effort, we have developed the multiscale framework MuMMI for accessing ensemble averages and very long time behavior of these lipid-protein systems at atomistic levels of detail.We present the GridSim2D component of that framework: a continuum level simulation capability that can address the very long time and large-scale behavior of lipid bilayers and associated proteins. The formulation follows a dynamic density function theory approach and can be parametrized entirely from molecular dynamics simulations, making it as consistent as possible to underlying molecular forcefields. Using this approach, we can simulate a bilayer microns in diameter for hundreds of milliseconds. The implementation uses special numerical algorithms to limit communication bandwidth and allow efficient time-integration of equations of motion. It is parallelized using OpenMP and MPI and is scalable to tens of thousands of cores.This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344. LLNL-ABS-815246.