Vibrational contribution to the sub-terahertz dielectric response of kinesin and its hydration shell.

The ability of proteins to change conformation underlies both their biological function and their use in bio-nanoelectromechanical systems as molecular machines and transducers. These conformational transitions are suggested to be facilitated by global physical vibrational modes in the sub-THz frequency range. However, direct experimental detection of these modes is difficult to achieve due to their weak spectroscopic signatures and strong water background. Thus, computational approaches fill knowledge gaps, help steer and interpret experiments. In this study, we used molecular dynamics simulations combined with normal mode analysis to explore the vibrational modes of an all-atom model of the globular motor domain of protein kinesin. We explored the coupling of these modes, via the corresponding modal dipole variation, to the electromagnetic field and predicted the resulting dielectric properties and absorption spectra in absolute units. We found that the inclusion of a water layer in the system leads to a blue-shift and reduced amplitude in the absorption spectra in the low-frequency (0-400 GHz) region. Further decomposition of absorption spectra into protein and water components showed non-additive behavior, arising from partially antiparallel dipole variation vectors of the protein and water fractions, which reduced the overall absorption. Comparison showed that the tubulin heterodimer has stronger absolute sub-THz absorption, consistent with its larger molecular weight and, hence, higher number of atoms and degrees of freedom than kinesin. Together, these results provide a mechanistic understanding of hydration effects on vibrational modes and dielectric properties of proteins. In a greater context, the results have implications for methods in bio-nanoelectromechanical systems for protein dynamics and conformation sensing and in biomedicine and bioelectromagnetics for electromagnetic field-mediated functional modification of proteins.