Studies in Molecular Recognition

分子识别研究

• 批准号: 9707870
• 负责人: W. Clark Still
• 金额: $ 66.6万
• 依托单位: Columbia University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-12-15 至 2000-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9707870&HistoricalAwards=false
• 关键词: Studies; Molecular; Recognition

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.

这项研究的重点有两个。 首先，合成将用于制备小分子受体的例子，先例表明这些受体将是选择性肽结合剂，然后筛选它们与大约的组合文库的结合。一万种不同的三肽或六肽。 显示出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对复杂分子系统的填充状态进行平均所涉及的采样问题，特别是具有许多不同的低能量形式或构象异构体的分子系统。 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。通过这一续签奖项，有机和高分子化学项目正在支持哥伦比亚大学化学系 W. Clark Still 博士的研究。 Still 博士的工作重点是设计和制备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涉及化学传感、化学分离和催化的实际应用中都具有潜在价值。该研究采用两种不同的方法：一种是在受体设计中使用组合方法的实验方法，另一种是涉及自由能计算的理论方法。