All-Atom Simulation and Coarse-Grained Analysis of the Rigor Actomyosin System

Abstract

Interactions of actin filaments with myosin motor proteins are important for a variety of cellular functions. The myosin mechanochemical cycle is a complicated sequence of steps including ATP hydrolysis by myosin, binding and unbinding of myosin with actin, and phosphate release from myosin during the force-producing “powerstroke.” No high-resolution crystal structure of actomyosin exists, however low resolution data from cryo-EM has allowed a characterization of the rigor state (ATP free) of actomyosin at an atomic level of detail. Here we present the first simulation study at an all-atom level of detail of the myosin II S1 domain in the rigor state interacting with a fully periodic actin filament. Additionally, we study myosin II in the rigor and post-rigor states in the absence of actin. Through a combination of all-atom level and coarse-grained (CG) analysis, we are able to identify effects of myosin binding on the actin filament, the effects on myosin dynamics of being bound to actin, and differences in the collective motions between simulated myosin states. CG level analysis allows further characterization of the influence of myosin binding on the definitions of domains which exhibit collective motion for the actin monomers in the periodic filament, and the identification of CG domains of myosin which interact strongly with actin domains based on a heterogeneous elastic network model analysis.