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Proc Natl Acad Sci U S A. 2017 Feb 28;114(9):2259-2264. doi: 10.1073/pnas.1700318114. Epub 2017 Feb 13.

Simulating the dynamics of the mechanochemical cycle of myosin-V.

Author information

1
Department of Chemistry, University of Southern California, Los Angeles, CA 90089.
2
Department of Chemistry, University of Southern California, Los Angeles, CA 90089 warshel@usc.edu.

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.

KEYWORDS:

brownian ratchet; chemomechanical coupling; cytoskeleton; molecular motors; powerstroke

PMID:
28193897
PMCID:
PMC5338489
DOI:
10.1073/pnas.1700318114
[Indexed for MEDLINE]
Free PMC Article

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