Studies in Molecular Recognition

我们的目标是设计新的构象均一的、对映体选择性的受体，用于功能化的、手性的有机分子，如多肽。根据以前的工作，这些受体将由现成的材料合成，预计将在对映体客体之间显示出高度的区别。这些分子可能形成基于手性聚合物小球和简单过滤的实用拆分方法的基础。收集的结合数据对于测试用于预测结合性质的计算方法也将是有价值的。这样的预测对于真正合理的分子设计至关重要。为了使用自由能模拟进行可靠的预测，最近的结果表明，可能有必要进行不切实际的长时间模拟。因此，将设计新的方法来极大地加速收敛到稳定的自由能。这些改进将包括开发有用的和更现实的连续统溶剂化模型，以及混合动力学/蒙特卡罗模拟方法。有了这个奖项，有机合成计划将支持仍然在哥伦比亚大学的W.Clark博士的研究。对映选择性受体的合成将在理论考虑的指导下进行。这将使化学家能够分离出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为合成生物化学和医学所需的日益复杂的物质提供一个重要工具，就像在化学工业中一样。

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.