Wetting of the Protein Active Site Leads to Non-Marcusian Reaction Kinetics

Enzymes exist in continuously fluctuating water bath dramatically affecting their function. Water not only forms the solvation shell but also penetrates into the protein interior. Changing the wetting pattern of the protein’s active site in response to altering redox state initiates a highly nonlinear structural change and non-Gaussian electrostatic fluctuations at the active site. The free-energy surfaces of electron transfer are highly nonparabolic (non-Marcusian), as shown by atomistic molecular dynamics simulations of hydrated ferredoxin protein and by an analytical model in agreement with simulations. The reorganization energy of electron transfer passes through a spike marking equal probabilities of the wet and dry states of the active site. The activation thermodynamics affected by wetting leads to a non-Arrhenius, passing through a maximum, plot for the reaction rate vs the inverse temperature.