PROTEIN DESIGN BY DYNAMIC COMBINATORIAL CHEMISTRY

通过动态组合化学进行蛋白质设计

• 批准号: 7381411
• 负责人: MARTIN A CASE
• 金额: $ 1.69万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7381411
• 关键词: PROTEIN; DESIGN; DYNAMIC; COMBINATORIAL; CHEMISTRY

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Understanding the molecular process of protein folding was one of the goals of 20th century science. That it remains so in the 21st is testament to the intractability of the problem, and to the necessity of new approaches. In terms of its impact on human health, particularly with regard to the neurodegenerative diseases that result from protein misfolding, the importance of such understanding cannot be overstated. There is also an urgent need to understand protein folding to gain insight into enzyme function. Successful completion of the proposed research will determine which amino-acid sequences confer optimal folding stability on small globular proteins. All possible sequences will be interrogated using dynamic combinatorial assembly strategies to access the formidable number of molecules necessary. Analysis of the subset of optimally stable sequences will determine whether any robust sequence-stability relationships exist in small globular proteins. Data from the proposed activity will determine which amino acid sequences confer optimal protein folding stability. In addition to its obvious relevance to the medical community, such information will also be valuable to biophysicists and bioinformaticians. The presence or absence of robust sequence-stability relationships will allow a critical re-evaluation of algorithms that seek to predict protein structure from nucleotide sequences.

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。了解蛋白质折叠的分子过程是20世纪科学的目标之一。它在21世纪仍然如此，证明了问题的棘手，也证明了新方法的必要性。就其对人类健康的影响，特别是对蛋白质错误折叠引起的神经退行性疾病的影响而言，这种理解的重要性怎么强调都不为过。还迫切需要了解蛋白质折叠，以深入了解酶的功能。这项拟议研究的成功完成将确定哪些氨基酸序列对小球状蛋白具有最佳的折叠稳定性。所有可能的序列都将使用动态组合组装策略进行查询，以获取所需的大量分子。对最佳稳定序列的子集的分析将确定在小球状蛋白中是否存在任何稳健的序列稳定性关系。来自拟议活性的数据将确定哪些氨基酸序列提供最佳的蛋白质折叠稳定性。除了与医学界有明显的相关性外，这些信息对生物物理学家和生物信息学家也很有价值。强健的序列稳定性关系的存在或不存在，将允许对寻求从核苷酸序列预测蛋白质结构的算法进行关键的重新评估。