Mostarac Deniz, Trapella Mattia, Bertini Luca, Comez Lucia, Paciaroni Alessandro, De Michele Cristiano
Department of Physics, University of Rome La Sapienza, 00185 Rome, Italy.
Department of Physics and Geology, University of Perugia, 06123 Perugia, Italy.
Biomacromolecules. 2025 May 12;26(5):3128-3138. doi: 10.1021/acs.biomac.5c00176. Epub 2025 Apr 8.
G-quadruplexes are noncanonical DNA structures rather ubiquitous in the human genome, which are thought to play a crucial role in the development of the majority of cancers. Here, we present a novel coarse-grained approach in modeling G-quadruplexes that accounts for their structural flexibility. We apply it to study the polymeric properties of G-quadruplex multimers, with and without crowder molecules, to mimic in vivo conditions. We find that, contrary to some suggestions found in the literature, long G-quadruplex multimers are rather flexible polymeric macromolecules, with a local persistence length comparable to monomer size, exhibiting a chain stiffness variation profile consistent with a real polymer in good solvent. Moreover, in a crowded environment (up to 10% volume fraction), we report that G-quadruplex multimers exhibit an increased propensity for coiling, with a corresponding decrease in the measured chain stiffness.
G-四链体是非典型的DNA结构,在人类基因组中相当普遍,被认为在大多数癌症的发展中起关键作用。在此,我们提出了一种新颖的粗粒度方法来对G-四链体进行建模,该方法考虑了它们的结构灵活性。我们将其应用于研究有无拥挤分子情况下G-四链体多聚体的聚合性质,以模拟体内条件。我们发现,与文献中的一些观点相反,长G-四链体多聚体是相当灵活的聚合大分子,其局部持久长度与单体大小相当,表现出与处于良溶剂中的真实聚合物一致的链刚度变化曲线。此外,在拥挤环境(体积分数高达10%)中,我们报告G-四链体多聚体表现出更高的卷曲倾向,同时测量到的链刚度相应降低。