G-四链体（G4）是一种特殊的与疾病过程密切相关的核酸二级结构。G4嵌套结构（G4NS），一种构象多态性现象，被证实在癌症相关基因启动子区广泛存在，且参与调控多个原癌基因表达。但是，目前对这一现象背后的分子机制了解甚少。因此，本项目尝试对G4NS的构象切换现象、其背后的普遍规律以及潜在的生物学功能展开研究。首先，研究G4NS构象切换的动态过程，通过分子动力学模拟探索构象转换细节，并确定影响构象稳定性的关键位点。其次，分析G4NS构象形成与转换的一般性规律，归纳其空间构象的约束条件，实现其构象预测的算法。最后，在全基因组范围内统计分析该结构的分布情况，研究关键位点的突变/修饰对结构，进而对基因表达的影响，从而挖掘G4NS的潜在生物学功能。本项目对于深刻认识以G4NS为代表的G4结构多态性和动态过程，理解其生物学功能机制，具有重要意义，并将为以G4为靶点的药物研发提供理论支撑和有效工具。

G-quadruplex (G4) is a special nucleic acid secondary structure involved in many important biological processes. The enrichment of G4 in promoters of the human genome has been shown to be closely related to disease processes. G4 Nested Structures (G4NS), a kind of conformational polymorphism, were found widespread in the promoters of cancer-related genes and participate in expressional regulation of multiple oncogenes. However, little is known about the molecular mechanism of this phenomenon. .In this project, we will study the conformational transition of G4NS, focusing on the rules of the transition and their potential biological functions. Firstly, the details of the dynamic process of the conformational transition will be explored by molecular dynamics simulation. The mechanism of the transition and the key sites influencing the conformational stability will be analyzed. Secondly, based on the mechanism and general rules of G4NS conformation, constraints for the spatial conformation will be proposed, and an algorithm will be implemented for predicting G4NS conformations. Finally, the distribution of G4NS will be analyzed throughout the human genome, and the impact of specific structural factors and the key site mutations/modifications on gene expression will be explored, for the purpose of explaining the potential biological function of G4NS. .This project is of great significance for deeply understanding the polymorphism and dynamic process of G4 structures represented by G4NS, and understanding their biological functions and mechanisms, and will provide theoretical support and effective tools for the designment of drugs targeting G4.