Dynamic Modeling of Myosin VI Allosteric Communication Pathway

Myosin VI, fueled by ATP hydrolysis, can act as a transport motor that moves along actin filaments to deliver cargo. It has been well established that the ATPase kinetics of the motor is affected by myosin VI binding to actin filaments. In order to investigate the origin of this dynamic change at a molecular level, we modeled both a myosin VI monomer and myosin VI actin complex by mapping their structures onto elastic networks. We analyzed the vibrational dynamics of the models and calculated the residue-dependent responses to local perturbations to map the corresponding allostery wiring diagrams. Specifically, we study the ADP to APO transition in both models. We report actin binding-induced changes in dynamics of the models and in the allosteric signaling network.