It remains unclear how the chemistry of certain compounds causes them to taste "sweet." Most studies have addressed how certain molecular substructures of the stimulus molecule should match certain molecular properties of binding sites on the cell surfaces. But some compounds taste sweet without having the presumed important features, and some compounds that have the prescribed features do not taste sweet. This project will use a novel approach utilizing the full three-dimensional structure of tastant molecules and receptor sites, instead of having a focus on just a particular substructure or functional group on the molecule. Five classes of compounds known to have sweet or bitter taste to humans will be studied. Computational facilities will analyze how the electrostatic fields of a whole molecule may interact with the receptor site before the actual "binding" occurs, and determine an optimal orientation of the molecule to fit the receptor site. Knowledge of the relation between molecular structure and biological function is basic to the understanding of how various systems such as receptors, ion channels, and enzymes work, and results from this study will have broad impact on all those fields. This project also has a strong undergraduate component that will considerably enhance the scientific quality of education at the institutions involved.
