The computational methods are applied to compare the electron-transfer probability for two distinct crystal structures of the Escherichia coli protein WrbA, an FMN-dependent NAD(P)H:quinone oxidoreductase, with the bound substrate benzoquinone. The computational methods were based on the combination of quantum mechanics/molecular mechanics approach, semi-empirical methods and quantum mechanical (QM) calculations of charge transfer rates using Marcus equation. The calculations indicate that the position of benzoquinone in a new structure reported here and solved at 1.33 Å resolution is more likely to be relevant for the physiological reaction of WrbA than a previously reported crystal structure [1] in which benzoquinone is shifted by ~5 Å. Because the true electron-acceptor substrate for WrbA is not yet known, the present results can serve to constrain computational docking attempts with potential substrates that may aid in identifying the natural substrate(s) and physiological role(s) of this enzyme. The approach used here highlights a role for QM calculations in crystal structure interpretation.
This work was supported by the Czech Science Foundation (project no GA15-12816S).