A structural perspective on the dynamics of kinesin motors

TL;DR

This paper presents a structural and thermodynamic analysis of kinesin motor dynamics, emphasizing the role of structural changes and the neck-linker in force generation and regulation, supported by molecular simulations and theoretical insights.

Contribution

It introduces a structure-based thermodynamic cycle for kinesin, clarifies motor directionality, and links structural changes to work production in biomolecular machines.

Findings

Kinesin's force generation involves structural changes and neck-linker dynamics.

A thermodynamic cycle for kinesin is proposed, highlighting mechanical and regulatory roles.

Structural change is essential for work production, akin to macroscopic heat engines.

Abstract

Despite significant fluctuation under thermal noise, biological machines in cells perform their tasks with exquisite precision. Using molecular simulation of a coarse-grained model and theoretical arguments we envisaged how kinesin, a prototype of biological machines, generates force and regulates its dynamics to sustain persistent motor action. A structure based model, which can be versatile in adapting its structure to external stresses while maintaining its native fold, was employed to account for several features of kinesin dynamics along the biochemical cycle. This analysis complements our current understandings of kinesin dynamics and connections to experiments. We propose a thermodynamic cycle for kinesin that emphasizes the mechanical and regulatory role of the neck-linker and clarify issues related the motor directionality, and the difference between the external stalling force and the internal tension responsible for the head-head coordination. The comparison between the thermodynamic cycle of kinesin and macroscopic heat engines highlights the importance of structural change as the source of work production in biomolecular machines.