 Blebistatin is a promising allosteric modulator for targeting myosin-2 motors, but its potency varies among different myosin-2 isoforms. This variation is due to differences in the probability of the binding pocket opening, which can be accurately predicted using Markov state models, MSMs, derived from molecular dynamic simulations. These MSMs also allow us to accurately predict the potency of other compounds for myosin-2 isoforms, providing a powerful tool for developing new drugs for treating diseases caused by myosin-2 mutations. This article was authored by Atomella, Jeffrey M. Lothammer, Louis G. Smith, and others.