Solvent Viscosity Effect on Protein Dynamics: Updating the Concepts

It is generally accepted that the structural dynamics of proteins in solution plays an important role in achieving and regulating the biochemical functions of the proteins. The microscopic picture of the dynamics is extremely complicated and includes relaxation times that extend over a very wide range. The continuous interaction of the protein structure with the surrounding water is well known to be intimately linked with this type of structural dynamics. By what mechanisms does the solvent affect protein dynamics? A possible experimental answer is to find what property of the solvent affects protein dynamics. The Brownian theory suggests that this property is the internal friction associated with the molecular motion, which is linked to the diffusion constant and the solvent viscosity. The role of the solvent viscosity in chemical kinetics was derived by Kramers in 1940 [1]. This result, which contradicted the widely used transition state theory, was overlooked for many years. The application of Kramers’s theory to protein reactions was suggested and demonstrated by Gavish in 1978 and 1979 [2,3]. Since then, many studies documented the solvent viscosity effect on biochemical reactions. Reaction rates, however, were found to display power-law dependence on viscosity (0 > power > - 1) instead of varying linearly with 1/viscosity, as predicted by Kramers. Independently, Grote and Hynes published in 1980 a theory of chemical reactions [4], which showed that Kramers’s and the transition state theories represent extreme cases of a more realistic situation. The Grote-Hynes theory necessitates the use of frequency-dependent friction, which seems to be responsible for the weaker dependence of the rate coefficients on the solvent viscosity observed also in nonbiological reactions. On the other hand, frequency dependence of the solvent viscosity is well known to be associated with the molecular dynamics of real liquids. Another aspect of the concept viscosity is linked with local volume fluctuations in liquids, which in densed liquids depend on the free volume available for translatory motion. In the presence of a solute, the rate of the solute structural rearrangements depends on the solvent viscosity in a power-law way, as shown theoretically and experimentally by Gegiou et al. [5].