Epistasis is a deviation from simple additivity in the measured mutational effects in protein systems. This usually arises from complex interactions between mutated residues, and in the case of double mutations can be represented in terms of free energy differences: ε = DDG 1,2 -(DDG 1 þ DDG 2 ). Previous studies have been able to classify epistasis for pairs of mutations, however, a general mechanistic description has yet to be determined. In this study, we use physical characteristics of the mutated residues with structural features of the proteins to explain observed epistasis. A model selection procedure was used based on data from the largest, most diverse, publicly available databases. Our resulting model can explain some of the observed epistasis and it consists of physically reasonable features such as charge and alpha carbon separation. These results will help in developing new methods and predictors for epistasis, and highlights the need for larger, more diverse datasets.
of the bimolecular quenching rates between the tryptophan triplet state and cysteine, in aqueous solution, is so far lacking. This limits the application of PET. We present a careful experimental and theoretical study of bimolecular quenching rates, measured in aqueous solution, as a function of viscosity and temperature, via time-resolved transient absorption. We obtain both the reaction-limited (k ET) and diffusion-limited (k D) contributions to the quenching rate at different temperatures. The resulting activation energy for k ET is found to be 4.5Kcal/mol. When comparing to theory, we find that the measured rates cannot be described by nonadiabatic ET. A quantitative description of the rates is achieved when longitudinal dielectric relaxation time is used in the rate expression, accounting for solvent dynamical control. Our data clearly show that solvent reconfiguration dynamics contributes significantly to the ET process in solution, and cannot be ignored.
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