Large-Scale All-Electron Quantum Chemical Calculation Toward a Sweet-Tasting Protein, Brazzein, and Its Mutants

Abstract

It had been recognized for many years that only small molecules were capable of causing a sweet taste. The search for sweeteners, however, found out naturally occurring sweettasting macromolecules, namely sweet proteins, in a variety of West African and South Asian fruits. Thaumatin was first identified as one of the sweet proteins, and then monellin, mabinlin, pentadin, curculin, brazzein, and neoculin were isolated sequentially. Sweet-tasting proteins are expected to be a potential replacement for natural sugars and artificial sweeteners. The human sweet taste receptor is a heterodimer of two Gprotein coupled receptor subunits, T1R2 and T1R3, and broadly responsive to natural sugars, artificial sweeteners, D-amino acids, and sweet-tasting proteins. The three-dimensional structure of the sweet receptor protein T1R2/T1R3 is still unknown, and the exact mode for interaction of sweet-tasting proteins with the T1R2/T1R3 receptor has not yet been elucidated. Very recently the recognition patterns of T1R2/T1R3 for small molecular sweeteners were suggested [1]. We have recently been carrying out computational simulations for saccharides and sweet-tasting proteins [2, 3]. The purpose of this study is to clarify characteristics of sweettasting materials and their functions and to search highly functional materials for foods and pharmaceutical agents on the basis of electronic state calculations. This work also aims to elucidate the mechanism for the expression of sweetness. A small protein, des-pGlu brazzein, is one of the sweetest protein sweeteners so far discovered and 4,000 times sweeter on a weight basis than a 2% sucrose solution. The protein is composed of a single polypeptide chain bearing 53 amino acid residues and four disulfide bonds [4]. To examine a relationship between the sweetness of protein sweeteners and their electronic properties, we are currently working all-electron quantum chemical calculations on des-pGlu brazzein and two different mutants, Glu41Lys and Arg43Ala, using a density functional method program, ProteinDF. The former mutant is sweeter than the brazzein and the latter mutant has a taste like water.