Bertini Luca, Trapella Mattia, Mostarac Deniz, Libera Valeria, Petrillo Caterina, De Michele Cristiano, Comez Lucia, Paciaroni Alessandro
Department of Physics and Geology, University of Perugia, via Alessandro Pascoli, 06123 Perugia, Italy.
Department of Physics, University of Rome La Sapienza, 00185 Rome, Italy.
J Phys Chem Lett. 2025 Jun 5;16(22):5435-5440. doi: 10.1021/acs.jpclett.5c01100. Epub 2025 May 22.
G-Quadruplexes are secondary structures that may form in G-rich nucleic acid sequences. The extended overhang at the ends of human telomeres has the potential to form multiple G-Quadruplexes that are crucial in regulating key biological processes. Here, we employ small-angle X-ray scattering-guided extremely coarse-grained simulations to provide a picture of the arrangement of G-Quadruplexes in long telomeric sequences. We observe significant destabilizing interactions between G-Quadruplexes, thus making the stacked conformation less prevalent. A helix-coil model is proposed to analytically describe the stacking-unstacking equilibrium within G-Quadruplex multimers and predict the occurrence of stacked and unstacked G-Quadruplex multiplets in arbitrarily long sequences.
G-四链体是可能在富含鸟嘌呤的核酸序列中形成的二级结构。人类端粒末端的延伸悬端有形成多个G-四链体的潜力，这些G-四链体在调节关键生物学过程中至关重要。在此，我们采用小角X射线散射引导的极粗粒度模拟，以呈现长端粒序列中G-四链体的排列情况。我们观察到G-四链体之间存在显著的去稳定相互作用，因此堆叠构象不太常见。我们提出了一个螺旋-线圈模型，以分析性地描述G-四链体多聚体中的堆叠-解堆叠平衡，并预测任意长序列中堆叠和未堆叠的G-四链体多重体的出现情况。
