Abstract
The nature of the conversion of chemical energy to directional motion in myosin V is examined by careful simulations that include two complementary methods: direct Langevin Dynamics (LD) simulations with a scaled-down potential that provided a detailed time-resolved mechanism, and kinetic equations solution for the ensemble long-time propagation (based on information collected for segments of the landscape using LD simulations and experimental information). It is found that the directionality is due to the rate-limiting ADP release step rather than the potential energy of the lever arm angle. We show that the energy of the power stroke and the barriers involved in it are of minor consequence to the selectivity of forward over backward steps and instead suggest that the selective release of ADP from a postrigor myosin motor head promotes highly selective and processive myosin V. Our model is supported by different computational methods-LD simulations, Monte Carlo simulations, and kinetic equations solution-as well as by structure-based binding energy calculations.