THEORY AND MODELING OF NONCOVALENT BINDING

描述：溶液中分子的非共价缔合是 在生物学和医学中的重要性。特别是，许多药物 通过与特定蛋白质靶点结合发挥作用。例如，一类重要的 艾滋病药物通过结合并抑制HIV-1的功能发挥作用 蛋白酶，一种对艾滋病病毒的生长至关重要的酶。因此，在本发明中， 旨在开发新药物的研究项目通常围绕 发现结合靶蛋白的分子。本项目旨在 发展理论和方法，促进药物设计的这一步， 更好地理解非共价键的物理机制 绑定，并通过创建算法和计算机程序，可以用来 预测哪些分子将与选定的分子靶结合。 本项目的具体目标包括阐明理论联系 结合亲和力测定的分子模拟; 一类有前途的新算法计算结合自由能; 胶订用溶剂效率模型的分析与改进 计算;以及根据实验数据验证新模型。

DESCRIPTION: The noncovalent association of molecules in solution is of fundamental importance in biology and medicine. In particular, many medications work by binding to specific protein targets. For example, an important class of AIDS medications works by binding to and inhibiting the function of HIV-1 protease, an enzyme that is essential for the growth of the AIDS virus. Thus, research projects aimed at developing new medications often center around the discovery of molecules that bind a targeted protein. The present project seeks to develop theory and methods that will facilitate this step in drug-design, by developing a better understanding of the physical mechanisms of noncovalent binding, and by creating algorithms and computer programs that can be used to predict what molecules will bind to a selected molecular target. The specific aims of this project include elucidation of the theory connecting molecular simulations with measured binding affinities; further development of a promising new class of algorithms for computing binding free energies; analysis and improvement of efficient models of the solvent for use in binding calculations; and validation of the new models against experimental data.