Determination of ab initio conformational shifts

从头算构象转变的测定

• 批准号: 6793185
• 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/6793185
• 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-阿根廷的圣路易斯大学与豪尔赫·A·维拉合作进行，作为国家卫生研究院资助号：GM-14312的延伸。 蛋白质和多肽的构象位移，定义为13Calpha和13Cβ化学位移与其相应的统计线圈值的偏差，可以在结构分析中以许多不同的方式使用。可能的应用包括：(I)二级结构映射；(Ii)生成结构约束；(Iii)三维结构细化；以及(Iv)三维结构生成。核磁共振数据的如此广泛的能力可以在确定溶液中的蛋白质结构方面发挥重要作用，并导致可能的广泛的理论应用。特别是，这一建议将侧重于对模型肽在中性pH下在水中的13C(和13C(化学位移))的Boltzmann平均值的量子化学计算，以及借助13C核磁共振化学位移信息预测蛋白质的三级结构。为了有效地实现这些目标，将引入一种新的协议来更有效地探索可访问的构象空间。预计这项研究的结果可能对基于知识的方法和用于预测球状蛋白质结构的从头算方法都有用，并可能有助于我们理解统计卷曲状态如何与更有结构的状态的构象偏好相互关联，例如α-螺旋和β-折叠构象。虽然将化学位移信息转换为可量化的结构信息是一个相对较新的领域，但本研究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。