Theoretical descriptors for the quantitative rationalisation of plastocyanin mutant functional propertiess

A quantitative rationalisation of the effect of specific amino acids on the recognition process and redox characteristics of plastocyanin towards cytochrome f, as determined by point mutation experiments, has been attempted in this study. To achieve this goal we derived theoretical descriptors directly from the three-dimensional structure of the plastocyanin mutants, in the same manner as it is usually done for small drug-like molecules. The protein descriptors computed can be related to: (a) the electrostatic and dipole-dipole interactions, effective at long distance; (b) polar interactions whose features are encoded by charged partial surface area descriptors; (c) the propensity of the surface residues to form hydrogen bonding interactions; and (d) dispersion and repulsive interactions. Moreover, an estimation of mutation-dependent variation of redox potential observed has been obtained by electrostatic free energy calculations. The quantitative structure-activity relationship (QSAR) models offer structural interpretation of the point mutation experiment responses and can be of help in the design of new protein engineering experiments.