nonlinearity of mechanochemical motions in motor proteins机械运动的非线性运动的蛋白质.pdfVIP

Nonlinearity of Mechanochemical Motions in Motor Proteins 1¤ 1 2 Yuichi Togashi *, Toshio Yanagida , Alexander S. Mikhailov 1 Nanobiology Laboratories, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, Japan, 2 Department of Physical Chemistry, Fritz Haber Institute of the Max Planck Society, Berlin, Germany 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 yields an approximation of strongly nonlinear dynamics. Citation: Togashi Y, Yanagida T, Mikhailov AS (2010) Nonlinearity of Mechanochemical Motions in Motor Proteins. PLoS Comput Biol 6(6): e1000814. doi:10.1371/ journal.pcbi.1000814 Editor: Willy Wriggers,