Studies in Molecular Recognition

目的是设计新的，构象均匀的， 官能化的手性有机化合物的对映选择性受体 分子如肽。 受体，那将是 由容易获得的材料合成，预计 显示对映体客体之间的高度区别，基于 以前的工作。 这样的分子可以形成 基于手性聚合物珠的实用拆分方法， 简单过滤。 收集的绑定数据也将 对测试预测的计算方法有价值 结合性能 这样的预测对于真正的 合理的分子设计 使用自由能模拟 可靠的预测，最近的结果表明， 可能需要长时间的模拟。 因此，新方法 将被设计为大大加速融合， 稳定的自由能 这些增强功能将包括 开发有用的和更现实的连续溶剂化 模型和混合动力学/蒙特卡罗模拟方法。 %%% 有了这个奖项，有机合成计划将支持 W博士的研究克拉克还在哥伦比亚大学。 的 将进行对映选择性受体的合成， 以理论为指导。 这将允许 分离手性分子的镜像形式。 大规模系统地进行这项工作的能力将 提供了一个重要的工具， 生物化学和医学中需要的复杂物质， 就像化学工业一样。

The objective is to design new, conformationally homogeneous, enantioselective receptors for functionalized, chiral organic molecules such as peptides. The receptors, that will be synthesized from readily available materials, are expected to show high distinctions between enantiomeric guests, based on previous work. Such molecules may form the basis of a practical resolution method based on chiral polymer beads and simple filtration. The binding data collected will also be valuable for testing the computational methods for predicting binding properties. Such predictions are crucial for truly rational molecular design. To use free energy simulations for reliable predictions, recent results suggest that impractically long simulations may be necessary. Consequently, new methods will be designed to accelerate dramatically the convergence to stable free energies. These enhancements will include the development of useful and more realistic continuum solvation models, and mixed dynamics/Monte Carlo simulation methods. %%% With this award, the Organic Synthesis Program will support the research of Dr. W. Clark Still at Columbia University. The synthesis of enantioselective receptors will be undertaken, guided by theoretical considerations. This will allow the chemist to separate the mirror image forms of chiral molecules. The ability to do this systematically on a large scale will provide an important tool to synthesize the increasingly complex substances needed in biochemistry and medicine, as will as in the chemical industry.