Exploring the myosin active/auto-inhibited state equilibrium by Markov state modeling

Abstract

Myosins are a ubiquitous class of molecular motors found in eukaryotes. Myosins play specialized roles in virtually every human cell. In fact, there are over 38 different myosin genes in the human genome. Due to their ubiquity, myosins have extensive clinical relevance as mutations in these proteins are often deleterious. For example, mutations in human β-cardiac myosin (MYH7) result in a spectrum of heart diseases called cardiomyopathies. Hypertrophic cardiomyopathy (HCM) is one of the leading causes of sudden cardiac death in the United States.