All-Electron Quantum Chemical Calculation toward Elucidation of Protein Function: Relationship between Electronic States of Sweet-Tasting Protein and its Sweetness

Abstract

We performed all-electron quantum chemical calculations based on the density functional method for des-pGlu brazzein, one of the sweetest protein, and six different mutants in order to examine a relationship between the sweetness of sweet-tasting proteins and their electronic properties such as electrostatic potential and frontier molecular orbitals, HOMO and LUMO. The calculated electrostatic potential maps for des-pGlu brazzein and two different sweet-tastting mutants showed that a number of amino acid residues including neutral amino acids, Tyr8 and Tyr51, have positive charge and especially for two mutants the positive charge widely spreads over each mutant. In addition, we found that some positively charged amino acid residues occur in the HOMO and/or LUMO of des-pGlu brazzein and two sweet-tasting mutants. A comparison of our computational results with experimental results on the sweetness of mutants suggests that the charged amino acid residues are involved in changing and/or eliciting the sweetness of des-pGlu brazzein. Our computations also indicate that the charged amino acid residues, the charge distribution and the property of HOMO and LUMO of sweettasting proteins can play important roles in the interaction between the proteins and the human receptor protein T1R2/T1R3.