title: Simulating the dynamics of the mechanochemical cycle of myosin-V.
abstract: The detailed dynamics of the cycle of myosin-V are explored by simulation approaches, examining the nature of the energy-driven motion. Our study started with Langevin dynamics (LD) simulations on a very coarse landscape with a single rate-limiting barrier and reproduced the stall force and the hand-over-hand dynamics. We then considered a more realistic landscape and used time-dependent Monte Carlo (MC) simulations that allowed trajectories long enough to reproduce the force/velocity characteristic sigmoidal correlation, while also reproducing the hand-over-hand motion. Overall, our study indicated that the notion of a downhill lever-up to lever-down process (popularly known as the powerstroke mechanism) is the result of the energetics of the complete myosin-V cycle and is not the source of directional motion or force generation on its own. The present work further emphasizes the need to use well-defined energy landscapes in studying molecular motors in general and myosin in particular.
authors.affiliation: Department of Chemistry, University of Southern California, Los Angeles, CA 90089.
authors.forename: Shayantani
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: Department of Chemistry, University of Southern California, Los Angeles, CA 90089.
authors.forename: Raphael
authors.initials: R
authors.lastname: Alhadeff
authors.affiliation: Department of Chemistry, University of Southern California, Los Angeles, CA 90089 warshel@usc.edu.
authors.forename: Arieh
authors.initials: A
authors.lastname: Warshel
mesh_terms: D000199:Actins / Q000737:chemistry* / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000737:chemistry* / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D001696:Biomechanical Phenomena; D006801:Humans; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D009010:Monte Carlo Method; D024701:Myosin Type V / Q000737:chemistry* / Q000378:metabolism; D010710:Phosphates / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D054730:Protein Interaction Domains and Motifs; D013816:Thermodynamics
chemical_list: D000199:Actins; D010710:Phosphates; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D024701:Myosin Type V
keywords: brownian ratchet; chemomechanical coupling; cytoskeleton; molecular motors; powerstroke