Studies in Molecular Recognition

本研究的重点是两个方面。 首先，合成将用于 准备小分子受体的例子， 将是选择性的肽结合剂，然后筛选它们的结合 与CA的组合文库。一万种不同的三或 六肽。 显示高序列选择性的受体设计将 然后用作受体库的基础。二是新 将开发模拟方法来处理采样 复杂分子布居态的平均化问题 系统，特别是具有许多不同的、低的 能量形式或构象。 开发的方法将用于 预测不同底物的相对结合自由能， 给定受体。有了这个更新奖，有机和高分子 化学计划正在支持W博士的研究。克拉克·斯蒂尔 哥伦比亚大学化学系。 斯蒂尔医生会集中精力 设计和制备合成的小分子受体 用于复杂的生物和化学基质。 此类小分子 受体具有潜在的价值，无论是在理解的基础上， 分子识别和涉及化学的实际应用 传感、化学分离和催化。该研究使用了两个 不同的方法：一个实验，使用组合方法， 受体设计和一个理论，涉及计算的自由 能量

The foci of this research are two fold. First, synthesis will be used to prepare examples of small molecule receptors that precedent suggests will be selective peptide binders and then screening them for binding with combinatorial libraries of ca. ten thousand different tri- or hexapeptides. Receptor designs that show high sequence selectivity will then be used as the basis of libraries of receptors. Second, new simulation methodology will be developed to deal with the sampling problem involved in averaging the populated states of a complex molecular system, in particular, a molecular system having many distinct, low energy forms or conformers. The methods developed will be used to predict relative binding free energies of different substrates for a given receptor. With this renewal award, the Organic and Macromolecular Chemistry Program is supporting the research of Dr. W. Clark Still of the Department of Chemistry at Columbia University. Dr. Still will focus his work on the design and preparation of synthetic, small molecule receptors for complex biological and chemical substrates. Such small molecule receptors have potential value both in understanding the basis of molecular recognition and in practical applications involving chemical sensing, chemical separations and catalysis. The research employs two different approaches: one experimental that uses combinatorial methods in receptor design and one theoretical that involves calculations of free energies.