Multiscale dynamic modeling of flexibility in myosin V using a planar mechanical model

Abstract

This paper presents a modification to the multiscale dynamic approach, introduced in [1]–[5], for the simulation and analysis of flexibility in motor proteins, especially myosin V. In the previous work, a new multiscale dynamic modeling approach has been developed that dissolves the issue of the long simulation run time that is due to the disproportionality between the small mass of myosin V relative to the large viscous drag coefficient. The interesting aspect of the approach is that it retains the mass properties, in contrast to the commonly used models which omit mass properties, at the nanoscale, to address the disproportionality issue. This paper discusses modeling flexibility in the protein as an extension of the original rigid multibody model. Adding flexibility to the mechanical model of motor protein creates an extra disproportionate issue between the mass (0.48ag), the viscous damping coefficient (108 ag/ms), and the stiffness constant (1014 ag.nm2/ms2) which cannot be handled by the original multiscale approach. The proposed modification helps to address the issue by introducing an extra scaling factor that brings all generalized active forces into proportion with the inertial terms. In order to show the effectiveness of the modified approach, a flexible mechanical model of myosin V is developed. Empirical studies have shown that myosin V's neck domain can be considered as three pairs of tandem elements called IQ motifs which can bend at junctures between them. Therefore, each neck is modeled by three rigid bodies connected by flexible pin joints together, rather than a single rigid body has been used in the previous works [1]–[5].