Suitable computational protocols for evaluating Stark shifts in proteins are yet to be established. In this work, we present a comprehensive computational method to predict the change in absorption frequency of a probe functional group as a direct result of a perturbation in its surrounding electrostatic field created by a protein environment, i.e., the Stark shift. We apply the method to human aldose reductase, a key protein enzyme that catalyzes the reduction of monosaccharides. We develop a protocol based on a combination of molecular dynamics and moving-domain QM/MM methods, which achieves quantitative agreement with experiment. The combined analysis of Stark effect spectroscopy and computational modeling is used to predict the protonation state of ionizable residues in the vicinity of the electrostatic probe.

QM/MM prediction of electric fields in the active site of proteins: Aiding the analysis of Stark shift measurements

246th National Meeting (2013)

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