PROTEIN DESIGN BY DYNAMIC COMBINATORIAL CHEMISTRY

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。了解蛋白质折叠的分子过程是世纪科学的目标之一。在21世纪仍然如此，证明了问题的棘手性，以及新方法的必要性。就其对人类健康的影响而言，特别是关于蛋白质错误折叠导致的神经退行性疾病，这种理解的重要性怎么强调都不过分。我们也迫切需要了解蛋白质折叠，以深入了解酶的功能。 成功完成拟议的研究将确定哪些氨基酸序列赋予小球状蛋白质最佳的折叠稳定性。所有可能的序列将使用动态组合组装策略进行询问，以获得所需的大量分子。最佳稳定序列的子集的分析将确定是否有任何强大的序列稳定性关系存在于小球状蛋白质。 来自拟定活性的数据将确定哪些氨基酸序列赋予最佳蛋白质折叠稳定性。除了与医学界明显相关外，这些信息对生物药理学家和生物信息学家也很有价值。存在或不存在强大的序列稳定性关系将允许一个关键的重新评估的算法，试图预测蛋白质结构的核苷酸序列。

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.