Optimizing a coarse-grained model for large-scale membrane protein simulation.

Abstract

Coarse-grained (CG) models are widely used to study membrane proteins at physiologically relevant scales. However, simulating long-range bilayer deformations induced by membrane-embedded proteins at submicrometer scales remains challenging. Here, we assess a generic solvent-free CG lipid model, previously applied to membrane proteins, for large-scale molecular dynamics simulations. We find that beyond a critical membrane size, the model becomes unstable due to membrane poration and unphysical undulations. To overcome this limitation, we systematically optimize this lipid model, significantly extending its stability for larger membrane systems. Using this improved model, we simulate membrane deformation induced by the mechanosensitive ion channel PIEZO in bilayers with varying mechanical properties. This optimized CG model with tunable mechanical properties provides a timely tool for investigating bilayer-mediated membrane protein interactions and bridging the gap between continuum elasticity theory and atomistic simulations.