FACTORS AFFECTING THE SECONDARY STRUCTURE IN PROTEINS

影响蛋白质二级结构的因素

• 批准号: 2444457
• 负责人: W C JOHNSON
• 金额: $ 17.18万
• 依托单位: OREGON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-12-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2444457
• 关键词: chemical aggregate; circular dichroism; colony stimulating factor; computer program /software; computer system design /evaluation; conformation; intermolecular interaction; muscarinic receptor; mutant; nonwater solvent; peptide chemical synthesis; protein folding; protein purification; protein sequence; protein structure; structural biology

DESCRIPTION: It is generally accepted that the amino acid sequence of a protein determines its ultimate three-dimensional structure. Researchers have noted that certain amino acids have a preference for a given secondary structure, and a number of schemes have been developed that use amino acid preferences to predict secondary structure from primary sequence. However, twenty years of research has led to little improvement over the original predictive schemes, and today theory remains about 70 percent accurate. During the last granting period, it was shown that in addition to considering the sequence of amino acids, the environment seen by the sequence (or bulk solvent in the peptides under study) must also be considered. Apparently, predictive algorithms must take the microsolvent of non-local amino acids in the tertiary structure into account when predicting secondary structure. The alpha-helix nucleation hypothesis was also investigated; a hypothesis that states that only a few residues with a strong propensity for alpha-helix structure initiate its formation and propagate the structure through indifferent sequences until strong breakers terminate the growth on both ends. The system investigated did not obey the nucleation hypothesis, indicating that the average propensity of near neighbors for secondary structure drive its formation. The first two specific aims listed here are the obvious sequels to the research carried out over the past granting period. The last specific aim continues the long standing interest of Dr. Johnson in relating the circular dichroism of proteins to their secondary structure, but this is a secondary goal. 1. It is proposed to investigate the conformational preferences of each amino acid in the solvent systems that have been used to stabilize alpha-helix and beta-strand structures. 2. It is proposed to investigate what changes in amino acid preferences are necessary for indifferent sequences to form an alpha helix or a beta-strand. 3. It is proposed to use circular dichroism to investigate the secondary structure of proteins of current interest, and to improve the system of analyzing CD for secondary structure.

描述：人们普遍认为，一种生物的氨基酸序列 蛋白质决定了其最终的三维结构。研究人员 已经注意到某些氨基酸对给定的次要氨基酸有偏好 结构，并且已经开发了许多使用氨基酸的方案 从一级序列预测二级结构的偏好。然而， 二十年的研究与最初的研究相比几乎没有什么进步。 预测性方案，今天的理论仍然大约70%准确。 在上一次授权期内，除 考虑到氨基酸的序列，我们看到的环境 序列(或正在研究的多肽中的散装溶剂)也必须是 考虑过了。显然，预测算法必须采用微溶剂 预测时考虑三级结构中的非本地氨基酸 二级结构。阿尔法螺旋成核假说也是 被调查的；一种假设，即只有几个残基具有 α-螺旋结构的强烈倾向启动了它的形成和 通过不同的序列传播结构，直到强断裂 终止两端的生长。被调查的系统不遵守 成核假说，表明近邻的平均倾向 二级结构的邻居推动了它的形成。前两个 这里列出的具体目标是这项研究的明显后续结果 在过去的授权期内。最后一个具体目标延续了漫长的 约翰逊博士在描述圆二向色性时的长期兴趣 蛋白质的二级结构，但这是次要目标。 1.建议研究每个分子的构象偏好 用于稳定的溶剂体系中的氨基酸 α-螺旋和β-链结构。2.建议调查 对于冷漠的人来说，氨基酸偏好需要什么变化 形成α螺旋或β链的序列。3.现建议 圆二色谱在蛋白质二级结构研究中的应用 目前的兴趣，并完善二手CD分析系统 结构。