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Determination of ab initio conformational shifts

从头算构象转变的测定

基本信息

批准号：
6923629
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
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-08-15 至 2007-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6923629
关键词：
carbon conformation globular protein nuclear magnetic resonance spectroscopy peptides protein folding protein protein interaction protein structure quantum chemistry

项目摘要

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的圣路易斯大学与 Jorge A. Vila 合作进行，作为 NIH 拨款号的延伸：GM-14312。蛋白质和肽构象位移被定义为 13Cα 和 13Cbeta 化学位移与其相应统计螺旋值的偏差，可以在结构分析中以多种不同方式使用。可能的应用包括：（i）二级结构映射； (ii) 产生结构性约束； (iii) 三维结构细化； (iv)三维结构生成。核磁共振衍生数据的如此广泛的能力可以在溶液中蛋白质结构的测定中发挥重要作用，并带来广泛的可能的理论应用。特别是，该提案将重点关注中性 pH 条件下水中所有天然氨基酸的玻尔兹曼平均值（分别为规范 α 螺旋和 β 折叠构象的模型肽）的 13C（和 13C（）化学位移的量子化学计算，以及借助 13C NMR 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。预计这项研究得出的结果可能对基于知识的方法和为预测球状蛋白结构而开发的从头算方法有用，并且可能有助于我们理解统计螺旋状态如何与更多结构状态的构象偏好相互关联，例如α螺旋和 β-折叠构象。尽管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，但这项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。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Coupling between conformation and proton binding in proteins.

蛋白质中构象与质子结合之间的耦合。

DOI：
10.1002/prot.20531
发表时间：
2005
期刊：
Proteins
影响因子：
2.9
作者：
Vila,JorgeA;Ripoll,DanielR;Arnautova,YelenaA;Vorobjev,YuryN;Scheraga,HaroldA
通讯作者：
Scheraga,HaroldA

Folding of the villin headpiece subdomain from random structures. Analysis of the charge distribution as a function of pH.