Analysis of electronic structure, binding, and vibrations in biotin-streptavidin complexes based on density functional theory and molecular mechanics.

In this work, the biotin-streptavidin complex was studied with density functional theory (DFT), molecular mechanical methods (MM), and a hybrid DFT/MM approach in order to obtain the theoretical predictions for electronic structures, binding, optical transitions, harmonic vibrations, and absorption spectra. It was demonstrated that biotin solvation in water can reduce the binding strength to streptavidin by more than half. All studied properties, including the biotin binding and the UV absorption of the biotin-streptavidin complex, are predicted to be protonation state dependent. The absorption edge of the complex calculated with TDDFT/MM was found to be virtually insensitive to the choice of the MM force field and strongly dependent on the type of embedding of the DFT partition. Both UV and terahertz light absorption spectra are predicted to be sensitive to the presence of biotin in the streptavidin tetramer.