Zernike Institute for Advanced Materials, University of Groningen, Groningen, The Netherlands.
Phys Chem Chem Phys. 2020 Dec 7;22(46):26944-26954. doi: 10.1039/d0cp04392c.
Introducing photoswitches into the DNA G-quadruplex provides excellent opportunities to control folding and unfolding of these assemblies, demonstrating their potential in the development of novel nanodevices with medical and nanotechnology applications. Using a quantum mechanics/molecular mechanics (QM/MM) scheme, we carried out a series of simulations to identify the effect of the size and substitution patterns of three azobenzene derivatives (AZ1, AZ2 and AZ3) on the excitation energies of the two lowest excited states of the smallest photoswitchable G-quadruplex reported to date. We demonstrated that the size and the substitution pattern do not affect the ultrafast cis-trans photoiomerization mechanism of the azobenzene derivatives significantly, in agreement with the experiment. However, molecular dynamics simulations revealed that while AZ2 and AZ3 G-quadruplexes are structurally stable during the simulations, the AZ1 G-quadruplex undergoes larger structural changes and shows two ground state populations that differ in the azobenzene backbone adopting two different conformations. AZ1, with para-para substitution pattern, provides more flexibility to the whole G-quadruplex structure compared to AZ2 and AZ3, and can thus facilitate the photoisomerization reaction between a nonpolymorphic, stacked, tetramolecular G-quadruplex and an unstructured state after trans-cis isomerization occurring in a longer time dynamics, in agreement with the experimental findings. The QM/MM simulations of the absorption spectra indicated that the thermal fluctuation plays a more crucial role in the main absorption band of the azobenzene derivatives than the inclusion of the G-quadruplex, implying that the influence of the G-quadruplex environment is minimal. We propose that the latter is attributed to the position of the azobenzene linkers in the G-quadruplexes, i.e. the edgewise loops containing the azobenzene moieties that are located above the G-quartets, not being fully embedded inside or involved in the stacked structure. Our theoretical findings provide support to a recent study of the photoresponsive formation of photoswitchable G-quadruplex motifs.
将光开关引入 DNA G-四链体为控制这些组装体的折叠和展开提供了极好的机会，这表明它们在开发具有医学和纳米技术应用的新型纳米器件方面具有潜力。我们使用量子力学/分子力学 (QM/MM) 方案进行了一系列模拟，以确定三种吖啶衍生物 (AZ1、AZ2 和 AZ3) 的大小和取代模式对迄今为止报道的最小光致可切换 G-四链体的两个最低激发态的激发能的影响。我们证明，大小和取代模式不会显著影响吖啶衍生物的超快顺反光异构化机制，这与实验结果一致。然而，分子动力学模拟表明，虽然 AZ2 和 AZ3 G-四链体在模拟过程中结构稳定，但 AZ1 G-四链体经历了更大的结构变化，并显示出两种不同的基态群体，其中吖啶部分采用两种不同的构象。与 AZ2 和 AZ3 相比，具有 para-para 取代模式的 AZ1 为整个 G-四链体结构提供了更大的灵活性，从而可以促进非多态、堆叠、四分子 G-四链体和非结构化状态之间的光致异构化反应在更长的动力学时间后发生顺式-反式异构化，这与实验结果一致。吸收光谱的 QM/MM 模拟表明，热波动在吖啶衍生物的主要吸收带中比包括 G-四链体的影响更重要，这意味着 G-四链体环境的影响最小。我们提出，后者归因于吖啶键联物在 G-四链体中的位置，即包含吖啶部分的边缘环位于 G-四联体之上，而不是完全嵌入或参与堆叠结构。我们的理论发现为最近关于光响应形成光致可切换 G-四链体基序的研究提供了支持。
