The Systematic Approach to Describing Conformational Rearrangements in G-quadruplexes

Conformational changes in DNA G-quadruplex-forming regions affect genome function and, thus, compose an interesting research topic. Computer modelling may yield insight into quadruplex folding and rearrangement, particularly molecular dynamics simulations. Here, we show that specific parameters, which are distinct from those commonly used in DNA conformational analyses, must be introduced for adequate interpretation and, most importantly, convenient visual representation of the quadruplex modelling results. We report a set of parameters that comprehensively and systematically describe G-quadruplex geometry in dynamics. The parameters include those related to quartet planarity, quadruplex twist, and quartet stacking; they are used to quantitatively characterise various types of quadruplexes and rearrangements, such as quartet distortion/disruption or deviation/bulging of a single nucleotide from the quartet plane. Our approach to describing conformational changes in quadruplexes using the new parameters is exemplified by telomeric quadruplex rearrangement, and the benefits of applying this approach to analyse other structures are discussed.

DNA G-四链体（G-quadruplex）形成区域的构象变化会影响基因组功能，因此成为极具研究价值的课题。计算机建模可为解析四链体的折叠与重排机制提供深入洞见，其中分子动力学模拟的应用尤为关键。本研究表明，相较于DNA构象分析中常用的参数体系，需引入特定参数方能实现对G-四链体建模结果的合理阐释，更重要的是实现便捷的可视化呈现。我们构建了一套可全面、系统描述动态过程中G-四链体几何结构的参数集。该参数集涵盖与G四分体平面性、四链体扭转以及四分体堆叠相关的各类参数，可用于定量表征不同类型的G-四链体及其重排过程，例如G四分体的畸变/断裂，或是单个核苷酸偏离或突出于四分体平面的情况。我们以端粒G-四链体重排为例，展示了利用这套新参数描述四链体构象变化的研究方法，并探讨了该方法应用于其他结构分析的潜在优势。