RUI: The Molecular Basis of Sweet Taste Recognition: A Computational Analysis

目前尚不清楚某些化合物的化学成分如何使它们尝起来“甜”。大多数研究已经解决了刺激分子的某些分子亚结构应该如何与细胞表面结合位置的某些分子特性相匹配的问题。但有些化合物尝起来是甜的，但没有假定的重要特征，而有些化合物具有规定的特征，但尝起来并不甜。这个项目将使用一种新的方法，利用味觉分子和受体位置的完整三维结构，而不是只关注分子上的特定亚结构或功能基团。五类已知对人类有甜味或苦味的化合物将被研究。计算设备将分析整个分子的静电场如何在实际的“结合”发生之前与受体位置相互作用，并确定分子的最佳取向以适应受体位置。了解分子结构和生物功能之间的关系是理解受体、离子通道和酶等各种系统如何工作的基础，这项研究的结果将对所有这些领域产生广泛影响。该项目还具有强大的本科生部分，这将大大提高有关机构的教育科学质量。

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.