Nonlinearity of Mechanochemical Motions in Motor Proteins

TL;DR

This study reveals that the common linear models of protein conformational motions are inadequate, especially for motor proteins like KIF1A, highlighting the need to reconsider fundamental assumptions in protein dynamics theories.

Contribution

The paper demonstrates the nonlinear nature of mechanochemical motions in motor proteins, challenging the traditional normal mode analysis approach.

Findings

Linear response assumption is deficient for ligand-induced motions.

Normal mode description fails for KIF1A's functional motions.

Nonlinear dynamics are essential for accurate protein motion modeling.

Abstract

The assumption of linear response of protein molecules to thermal noise or structural perturbations, such as ligand binding or detachment, is broadly used in the studies of protein dynamics. Conformational motions in proteins are traditionally analyzed in terms of normal modes and experimental data on thermal fluctuations in such macromolecules is also usually interpreted in terms of the excitation of normal modes. We have chosen two important protein motors - myosin V and kinesin KIF1A - and performed numerical investigations of their conformational relaxation properties within the coarse-grained elastic network approximation. We have found that the linearity assumption is deficient for ligand-induced conformational motions and can even be violated for characteristic thermal fluctuations. The deficiency is particularly pronounced in KIF1A where the normal mode description fails completely in describing functional mechanochemical motions. These results indicate that important assumptions of the theory of protein dynamics may need to be reconsidered. Neither a single normal mode, nor a superposition of such modes yield an approximation of strongly nonlinear dynamics.