多肽组装趋势的分子水平研究

Peptides and proteins are known to form a variety of ordred structures via assembling processes. The insight of the assemble peptide and protein structures could provide basis for developing diagnosis and therapeutics for neurodegenerative diseases. The documented experimental results have revealed that the capability of peptides to form ordered structures has significant dependence on the sequence. It is keen to investigate the site-specific effects due to the residues on the aggregation propensity of peptide molecules. An important subject under study is the formation mechanisms of peptide assemblies at the level of individual amino acids. This effort could lead to the insight of assembly propensity of peptide molecules. In this proposed project, we will investigate the assembly propensity of peptides based on the high resolution structural analysis of surface-bound peptide assemblies. Specifically, the dependence of the peptdie assembly structures on sequences will be systematically pursued, including the impact of amino acids on the adsorption stability and assembly propensity. The effects due to various mutations, including phosphorylation and glycosylation, will also be explored. It is anticipated that these efforts could advance our insight on the peptide assembly mechanisms, as well as provide the potential venues for developing novel diagnosis and therapeutic approaches twoards relevant diseases.

多肽和蛋白分子可以通过自组装过程形成多种有序结构,对于这些多肽和蛋白分子自组装结构的认识可以为发展与退行性疾病相关的检测和治疗方法提供重要基础。大量实验研究结果表明多肽分子形成有序结构的能力具有非常突出的序列依赖特征，关于氨基酸序列中残基的位置和组合方式的研究对在分子水平上认识多肽聚集机理的有至关重要的意义。这方面工作的一个重要内容是氨基酸残基水平上研究多肽分子的组装规律，并在此基础上实现对多肽分子组装趋势的认识和有效调控。本项目在对表面吸附多肽组装结构进行高分辨分析的基础上，研究多肽分子自组装结构与氨基酸序列的关联规律，揭示多肽序列中不同类型氨基酸对吸附稳定性和组装趋势的影响，并进一步研究序列中氨基酸突变（如磷酸化和糖基化）对多肽组装趋势的影响，探索在分子水平上理解多肽组装过程和调控规律，为与多肽组装有关的疾病诊治提供必要基础。

本项目在2017-2020年度期间根据项目的总体目标，围绕多肽分子聚集趋势和多肽分子间相互作用进行了深入研究。考察了氨基酸残基序列对于多肽聚集趋势的影响，并探索了多肽分子聚集趋势的分子机制。这些结果有助于认识多肽分子组装的机理，如氨基酸序列中残基的位置和组合方式对多肽组装趋势的贡献，以及认识不同氨基酸序列的动力学和热力学效应，并在此基础上实现对多肽分子组装趋势的有效调控。