Determination of ab initio conformational shifts

从头算构象转变的测定

• 批准号: 6683743
• 负责人: HAROLD A. SCHERAGA
• 金额: $ 3.36万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-15 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6683743
• 关键词: carbon; conformation; globular protein; nuclear magnetic resonance spectroscopy; peptides; protein folding; protein protein interaction; protein structure; quantum chemistry

DESCRIPTION (provided by applicant) This research will be carried out primarily in San Luis-Argentina at the San Luis University in collaboration with Jorge A. Vila as an extension of NIH Grant Number: GM-14312. Protein and peptide conformational shifts, which are defined as the deviations of the 13Calpha and 13Cbeta chemical shifts from their corresponding statistical-coil values, can be used in many different ways in structural analysis. Possible applications include: (i) secondary structure mapping; (ii) generating structural constraints; (iii) three-dimensional structural refinement; and (iv) three-dimensional structural generation. Such a wide capability of NMR-derived data could play an important role in determination of protein structure in solution, and lead to a broad scope of possible theoretical applications. In particular, this proposal will focus on both the quantum-chemical computation of the Boltzmann-averaged values of the 13C( and 13C( chemical shifts for all the naturally occurring amino acids in water at neutral pH for a model peptide in both the canonical alpha-helical and beta-sheet conformations, respectively, and on the prediction of the tertiary structure of proteins with the help of 13C NMR chemical shift information. To accomplish these goals efficiently, a new protocol to explore the accessible conformational space more efficiently will be introduced. It is expected that the results derived from this investigation may be useful for both knowledge-based approaches and ab initio methods developed to predict the structures of globular proteins, as well as may contribute to our understanding of how statistical-coil states can be inter-related with the conformational preferences of more-structured states, such as alpha-helical and beta-sheet conformations. Although the conversion of chemical shift information into quantifiable structural information is a relatively new field, the results provided by this proposed research would provide additional assistance for an accurate tertiary protein structure prediction and, consequently, make a significant contribution to the solution of the, as yet unsolved, protein folding problem.

描述（由申请人提供） 这项研究将主要在圣路易斯大学的圣路易斯 - 阿根廷与Jorge A. Vila合作，作为NIH赠款编号的扩展：GM-14312。 蛋白质和肽构象转移被定义为13钙和13cbeta化学偏移与相应统计线圈值的偏差，可以在结构分析中以许多不同的方式使用。可能的应用程序包括：（i）二级结构映射； （ii）产生结构性约束； （iii）三维结构改进； （iv）三维结构产生。 NMR衍生的数据的如此广泛的能力可以在确定溶液中的蛋白质结构中起重要作用，并导致广泛的理论应用范围。 In particular, this proposal will focus on both the quantum-chemical computation of the Boltzmann-averaged values of the 13C( and 13C( chemical shifts for all the naturally occurring amino acids in water at neutral pH for a model peptide in both the canonical alpha-helical and beta-sheet conformations, respectively, and on the prediction of the tertiary structure of proteins with the help of 13C NMR chemical shift information.为了有效地实现这些目标，将提出一种新的协议，以更有效地探索可访问的构象空间。 beta套件的构象。