Mechanism of Cardiac Tropomyosin Transitions on Filamentous Actin As Revealed by All-Atom Steered Molecular Dynamics Simulations

Michael R. Williams; Jil C. Tardiff; Steven D. Schwartz

doi:10.1021/acs.jpclett.8b00958

Mechanism of Cardiac Tropomyosin Transitions on Filamentous Actin As Revealed by All-Atom Steered Molecular Dynamics Simulations

Michael R. Williams, Jil C. Tardiff, Steven D. Schwartz

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

The three-state model of tropomyosin (Tm) positioning along filamentous actin allows for Tm to act as a gate for myosin head binding with actin. The blocked state of Tm prevents myosin binding, while the open state allows for strong binding. Intermediate to this transition is the closed state. The details of the transition from the blocked to the closed state and then finally to the open state by Tm have not been fully accessible to experiment. Utilizing steered molecular dynamics, we investigate the work required to move the Tm strand through the extant set of proposed transitions. We find that an azimuthal motion around the actin filament by Tm is most probable in spite of increased initial energy barrier from the topographical landscape of actin.

Original language	English (US)
Pages (from-to)	3301-3306
Number of pages	6
Journal	Journal of Physical Chemistry Letters
Volume	9
Issue number	12
DOIs	https://doi.org/10.1021/acs.jpclett.8b00958
State	Published - Jun 21 2018

ASJC Scopus subject areas

General Materials Science
Physical and Theoretical Chemistry

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title = "Mechanism of Cardiac Tropomyosin Transitions on Filamentous Actin As Revealed by All-Atom Steered Molecular Dynamics Simulations",

abstract = "The three-state model of tropomyosin (Tm) positioning along filamentous actin allows for Tm to act as a gate for myosin head binding with actin. The blocked state of Tm prevents myosin binding, while the open state allows for strong binding. Intermediate to this transition is the closed state. The details of the transition from the blocked to the closed state and then finally to the open state by Tm have not been fully accessible to experiment. Utilizing steered molecular dynamics, we investigate the work required to move the Tm strand through the extant set of proposed transitions. We find that an azimuthal motion around the actin filament by Tm is most probable in spite of increased initial energy barrier from the topographical landscape of actin.",

author = "Williams, {Michael R.} and Tardiff, {Jil C.} and Schwartz, {Steven D.}",

note = "Funding Information: We acknowledge the support of the NIH through Grant R01HL107046 Publisher Copyright: Copyright {\textcopyright} 2018 American Chemical Society.",

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AB - The three-state model of tropomyosin (Tm) positioning along filamentous actin allows for Tm to act as a gate for myosin head binding with actin. The blocked state of Tm prevents myosin binding, while the open state allows for strong binding. Intermediate to this transition is the closed state. The details of the transition from the blocked to the closed state and then finally to the open state by Tm have not been fully accessible to experiment. Utilizing steered molecular dynamics, we investigate the work required to move the Tm strand through the extant set of proposed transitions. We find that an azimuthal motion around the actin filament by Tm is most probable in spite of increased initial energy barrier from the topographical landscape of actin.

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Mechanism of Cardiac Tropomyosin Transitions on Filamentous Actin As Revealed by All-Atom Steered Molecular Dynamics Simulations

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