Studies in Molecular Recognition

这项研究的重点有两个方面。首先，合成将用于制备小分子受体的例子，先例表明这些小分子受体将是选择性肽结合物，然后筛选它们与大约一万个不同的三或六肽的组合文库结合。显示高序列选择性的受体设计将被用作受体文库的基础。其次，将开发新的模拟方法来处理复杂分子系统，特别是具有许多不同的低能量形式或构象的分子系统的平均填充状态的采样问题。所开发的方法将用于预测给定受体的不同底物的相对结合自由能。有了这个更新奖，有机和大分子化学项目支持哥伦比亚大学化学系W. Clark Still博士的研究。Still博士将专注于设计和制备用于复杂生物和化学底物的合成小分子受体。这种小分子受体在理解分子识别的基础以及在化学传感、化学分离和催化等实际应用中都具有潜在的价值。这项研究采用了两种不同的方法：一种是实验方法，在受体设计中使用组合方法，另一种是理论方法，涉及自由能的计算。

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.