Modeling Flexibility in Myosin V Using a Multiscale Articulated Multi-Rigid Body Approach

This paper presents a multiscale dynamic model for the simulation and analysis of flexibility in myosin V. A 3D finite segment model, a multirigid body model connected with torsional springs, is developed to mechanically model the biological structure of myosin V. The long simulation run time is one of the most important issues in the dynamic modeling of biomolecules and proteins due to the disproportionality between the physical parameters involved in their dynamics. In order to address this issue, the most-used models, based on the famous overdamped Langevin equation, omit the inertial terms in the equations of motion; that leads to a first order model that is inconsistent with Newton's second law. However, the proposed model uses the concept of the method of multiple scales (MMS) that brings all of the terms of the equations of motion into proportion with each other; that helps to retain the inertia terms. This keeps the consistency of the model with the physical laws and experimental observations. In addition, the numerical integration's step size can be increased from commonly used subfemtoseconds to submilliseconds. Therefore, the simulation run time is significantly reduced in comparison with other approaches. The simulation results obtained by the proposed multiscale model show a dynamic behavior of myosin V which is more consistent with experimental observations in comparison with other overdamped models.