BETA SHEET FORMATION IN A SIMPLE MODEL SYSTEM

描述：拟议的研究旨在了解能量学和 b片结构设计。 里根博士成功地开发了一种模型 系统，其中研究b片形成，基于一个变体的b1 IgG结合蛋白G（b1）的结构域。 b1是结构上的， 经化学充分表征的56个残基蛋白。 她可以容易 操纵编码它的基因并纯化大量的蛋白质。 在初步研究中，通过在溶剂中进行一系列取代， 暴露的位置，她已经确定了一个热力学规模为 氨基酸的b-折叠形成倾向。 根据这些 研究结果，她还测量了能量的成对相互作用之间 在H-键合的B-折叠的两条链上的氨基酸 绝佳的价钱 她的实验结果显示， 衍生概率 在目前的提案中，她继续执行两个额外的 成对研究：一个非氢键反平行位点和一个氢键 平行网站 在这些地点统计观察到的配对是 与她最初的研究有很大不同。 她会跟着 通过使用NMR方法来结构表征 稳定的相互作用。 最后，她将追求新颖的设计，以解决特异性与 蛋白质结构的稳定性，通过将b-折叠转化为a-螺旋，反之亦然 亦然 第一个这样的设计已经实现：一种蛋白质， 与b1的同一性百分比，但其采用螺旋构象。 进一步 这样的设计及其结构和热力学特性 提出了 她的研究成果将大大提高基础 理解b片结构的能量学和设计， 合理重新设计b表的基本规则。

DESCRIPTION: The proposed research seeks to understand the energetics and design of b-sheet structure. Dr. Regan has successfully developed a model system in which to study b-sheet formation, based on a variant of the b1 domain of IgG-binding protein G (b1). b1 is a structurally and thermodynamically well characterized 56 residue protein. She can readily manipulate the gene that encodes it and purify large quantities of protein. In preliminary studies, by making a series of substitutions at solvent exposed positions, she has determined a thermodynamic scale for the b-sheet-forming propensities of the amino acids. Building on these findings, she also measured the energetics of pair-wise interactions between amino acids across two strands of an anti-parallel b-sheet at an H-bonded site. Her experimental results show strong correlations with statistically derived probabilities. In the current proposal, she goes forward to perform two additional pair-wise studies: a non-H-bonded anti-parallel site and an H-bonded parallel site. The statistically observed pairings at such sites are significantly different from those of her original study. She will follow up on this work by using NMR methods to structurally characterize the nature of the stabilizing interactions. Finally, she will pursue novel designs to address specificity versus stability in protein structure, by converting b-sheet into a-helix and vice versa. The first such design has been realized: a protein that has 50 percent identity to b1, but which adopts a helical conformation. Further such designs and their structural and thermodynamic characterization are proposed. The results of her studies will significantly enhance fundamental understanding of the energetics and design of b-sheet structure and lay the ground rules for the rational redesign of b-sheets.