Elimination of bitter-off taste of stevioside through structure modification and computational interventions

Stevioside is a natural non-caloric sweetener obtained from Stevia rebaudiana Bertoni plant. The major challenge in the commercialization of stevioside as a natural sweetener is its bitter-off taste. In this study, we prepared molecular models of potential taste receptors of stevioside, both sweet and bitter. With appropriate modifications on the stevioside backbone, we performed molecular docking of prepared ligands with both sweet and bitter taste receptors. Based on binding energy, we found that one of the potential substituents, Kamiya-8, shows a good affinity towards sweet taste and a weak affinity for bitter receptors. Further, we selected Kamiya-8 for molecular dynamics simulations to improve the prediction of binding energy and to check the binding strength of Kamiya-8 with taste receptors. Moreover, we also performed MM-PBSA calculation for calculating the end state free energies of molecules in solvent and found that Kamiya-8 gives a 2-fold effect as it interacts with sweet receptors (T1R2, T1R3) with lowest binding energy conformation (-285.265 kcal/mol, -571.481 kcal/mol). Secondly, it gives high binding energy (-273.319 kcal/mol, -355.500 kcal/mol) with bitter taste receptors (T2R4, T2R14) as compared to stevioside. Based on this study, we found that Kamiya-8 can be the potential substituent that can improve the palatability of stevioside. (C) 2019 Elsevier Ltd. All rights reserved.