Kinesin motility driven by subdomain dynamics

  1. Wonmuk Hwang  Is a corresponding author
  2. Matthew Lang  Is a corresponding author
  3. Martin Karplus  Is a corresponding author
  1. Texas A&M University, United States
  2. Vanderbilt University, United States
  3. Harvard University, United States


The microtubule (MT)-associated motor protein kinesin utilizes its conserved ATPase head to achieve diverse motility characteristics. Despite considerable knowledge about how its ATPase activity and MT binding are coupled to the motility cycle, the atomic mechanism of the core events remain to be found. To obtain insights into the mechanism, we performed 38.5 microseconds of all-atom molecular dynamics simulations of kinesin-MT complexes in different nucleotide states. Local subdomain dynamics were found to be essential for nucleotide processing. Catalytic water molecules are dynamically organized by the switch domains of the nucleotide binding pocket while ATP is torsionally strained. Hydrolysis products are 'pulled' by switch-I, and a new ATP is "captured" by a concerted motion of the α0/L5/switch-I trio. The dynamic and wet kinesin-MT interface is tuned for rapid interactions while maintaining specificity. The resulting mechanism provides the flexibility necessary for walking in the crowded cellular environment.

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Author details

  1. Wonmuk Hwang

    Department of Biomedical Engineering, Texas A&M University, College Station, United States
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7514-3186
  2. Matthew Lang

    Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, United States
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
  3. Martin Karplus

    Department of Chemistry and Chemical Biology, Harvard University, Cambridge, United States
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.


National Institutes of Health (R01GM087677)

  • Wonmuk Hwang
  • Matthew Lang

PIttsburgh Supercomputing Center (Anton Supercomputer)

  • Wonmuk Hwang
  • Martin Karplus

Texas A&M Supercomputing Facility

  • Wonmuk Hwang

Texas Advanced Computing Center

  • Wonmuk Hwang

CHARMM Development Project

  • Martin Karplus

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Antoine M van Oijen, University of Wollongong, Australia

Version history

  1. Received: May 24, 2017
  2. Accepted: November 3, 2017
  3. Accepted Manuscript published: November 7, 2017 (version 1)
  4. Version of Record published: December 6, 2017 (version 2)


© 2017, Hwang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.


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  1. Wonmuk Hwang
  2. Matthew Lang
  3. Martin Karplus
Kinesin motility driven by subdomain dynamics
eLife 6:e28948.

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