Protein Structure/Function by Quantum Chemistry and NMR

通过量子化学和 NMR 分析蛋白质结构/功能

• 批准号: 6687821
• 负责人: Eric Oldfield
• 金额: $ 27.91万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-01-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6687821
• 关键词: Protein; Structure; Function; Quantum; Chemistry

DESCRIPTION (provided by applicant): The broad, long term objectives of this research are to use NMR and quantum chemical methods to learn more about protein structure and function and to apply these methods to protein structure prediction and refinement, including the topic of enzyme/inhibitor or drug/target interactions. The first specific aim is to compute NMR shielding surfaces for side-chains in amino acids; to calibrate these theoretical results versus experimental shielding tensors and orientations, and to incorporate these results into a Web Chemical Shift calculator, as well as the CNS program, for use in protein and peptide structure determination. Second, we will use combined multinuclear (1-H, 2-H, 17-O) NMR and quantum chemical methods to investigate hydrogen bonding and electrostatics in peptides and proteins. Third, we will use NMR, x-ray diffraction and quantum chemical methods to probe enzyme-inhibitor interactions, focussing on the bisphosphonate class of drugs which inhibit the enzymes farnesyl pyrophosphate and geranylgeranyl pyrophosphate synthase, and which have potent bone anti-resorptive, anti-cancer and anti-parasitic activity. The fourth and final specific aim is to use NMR and quantum chemical methods to develop improved approaches for quantitative structure-activity relationship studies (quantum QSAR applications).

描述（由申请人提供）：本研究的广泛，长期目标是使用NMR和量子化学方法来了解更多关于蛋白质结构和功能的信息，并将这些方法应用于蛋白质结构预测和改进，包括酶/抑制剂或药物/靶标相互作用的主题。第一个具体的目标是计算核磁共振屏蔽表面的侧链氨基酸，校准这些理论结果与实验屏蔽张量和方向，并将这些结果纳入网络化学位移计算器，以及CNS程序，用于蛋白质和肽的结构测定。第二，我们将结合使用多核（1-H，2-H，17-O）NMR和量子化学方法来研究多肽和蛋白质中的氢键和静电。第三，我们将使用NMR，X射线衍射和量子化学方法来探测酶抑制剂的相互作用，重点是双膦酸类药物，抑制酶法呢基焦磷酸和香叶基香叶基焦磷酸合酶，并具有强大的骨抗吸收，抗癌和抗寄生虫活性。第四个也是最后一个具体目标是使用NMR和量子化学方法来开发改进的定量构效关系研究方法（量子QSAR应用）。