Multiscale Simulation of Multiprotein Assemblies: The Challenges of Ultra-Coarse-Graining

Abstract

A multiscale theoretical and computational methodology will be described for studying biomolecular systems across multiple length and time scales, providing a systematic connection between molecular-scale interactions, coarse-grained models, and mesoscopic phenomena. At the heart of the approach is a methodology for deriving “ultra” coarse-grained models that embody the underlying molecular-scale interactions because the approach is based on systematic principles from statistical mechanics. However, a critical component of the methodology is also its connection to experimental structural data, such as cryo-EM or x-ray, when developing the ultra-coarse-grained models, thus making it “hybrid” in its character. Important results from our multiscale simulations will be presented that describe key features of large multiprotein complexes, such as the HIV-1 virus capsid, actin filaments, and (if time allows) protein-mediated remodelling of membranes.