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.
Highlights
Protein machines, which may represent enzymes, ion pumps or molecular motors, play a fundamental role in biological cells and understanding of their activity is a major challenge
It is often assumed that conformational dynamics of motor proteins is well described within a linear response approximation and corresponds to excitation of normal modes
The analysis of thermal fluctuations and the interpretation of the respective experimental structural data are traditionally performed assuming that fluctuations are linear and, correspond to thermal excitation of various normal modes
Summary
Protein machines, which may represent enzymes, ion pumps or molecular motors, play a fundamental role in biological cells and understanding of their activity is a major challenge. Operation of these machines is based on slow conformational motions powered by external energy supply, often with ligands (such as ATP). In molecular motors, binding of ATP and its subsequent hydrolysis induce functional mechanochemical motions, essential for their operation. These motions, which follow after an energetic activation, are conformational relaxation processes. There is no general justification to assume that relaxation processes in proteins are linear and this assumption has to be verified for particular macromolecules
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
