The Empirical Valence Bond (EVB) method is based on the calibration of the alpha-shift and the adiabatic coupling terms to reproduce the energetics of the reference reaction in solution in order to calculate the energetics of the same reaction but on a target environment (another solvent or within an enzyme), i.e., we use exactly the same gas-shift and off-diagonal terms that were calibrated for the reference environment to diagonalize the EVB matrix in order to solve the secular equation for the target environment. In this scheme, the solvation energy is recalculated by an iterative algorithm for the valence bond (VB) states in the target environment. The EVB states are indeed the microscopic equivalent of Marcus' parabolas. We have studied the DNA polymerase β in order to assess the catalytic effects of the two magnesium ions in the active site. Hence, free energy calculations by means of the EVB approach have been evaluated for the native and selected mutants (D256E and D192A). Overall, we have found that electrostatic effects have a critical role in the catalysis of both native and mutant enzymes.

Computational study on the catalytic role of the magnesium ions in the active site of the DNA Polymerase β

251st National Meeting (2016)

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