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） 这项研究将主要在阿根廷圣路易斯圣路易斯大学与Jorge A.合作进行。Vila是NIH资助号GM-14312的扩展。 蛋白质和肽的构象位移定义为13 C α和13 C β化学位移与其相应的螺旋值的偏差，可以以许多不同的方式用于结构分析。可能的应用包括：（i）二级结构映射;（ii）生成结构约束;（iii）三维结构细化;和（iv）三维结构生成。这种广泛的NMR衍生数据的能力可以在确定溶液中的蛋白质结构中发挥重要作用，并导致广泛的可能的理论应用。特别是，该建议将集中在量子化学计算的玻尔兹曼平均值的13 C（和13 C（化学位移的所有天然存在的氨基酸在水中，在中性pH值的典型的α-螺旋和β-折叠构象的模型肽，分别，和预测的蛋白质的三级结构的帮助下，13 C NMR化学位移信息。为了有效地实现这些目标，将引入一种新的协议，以更有效地探索可及构象空间。预计从这项调查中得出的结果可能是有用的知识为基础的方法和从头计算方法开发的球状蛋白质的结构预测，以及可能有助于我们了解如何螺旋线圈状态可以相互关联的构象偏好的更结构化的状态，如α-螺旋和β-折叠构象。虽然将化学位移信息转化为可量化的结构信息是一个相对较新的领域，但这项研究所提供的结果将为准确的蛋白质三级结构预测提供额外的帮助，从而为解决尚未解决的蛋白质折叠问题做出重大贡献。