Polêto Marcelo D, Lemkul Justin A
Department of Biochemistry, Virginia Tech, Blacksburg, VA 24061, United States.
Center for Drug Discovery, Virginia Tech, Blacksburg, VA 24061, United States.
bioRxiv. 2023 Aug 14:2023.08.10.552810. doi: 10.1101/2023.08.10.552810.
The formation of G-quadruplexes (GQs) occurs in guanine-rich sequences of DNA and RNA, producing highly stable and structurally diverse noncanonical nucleic acid structures. GQs play crucial roles in regulating transcription, translation, and replication; and maintaining the genome, among others, thus changes to their structures can lead to diseases such as cancer. Previous studies using polarizable molecular dynamics simulations have shown differences in ion binding properties between telomeric and TERRA GQs despite architectural similarities. Here, we used volume-based metadynamics and repulsive potential simulations in conjunction with polarizable force fields to quantify the impact of ion binding on GQ dynamics and ion binding free energies. Furthermore, we describe how GQs exert electric fields on their surroundings to link dynamics with variations in electronic structure. Our findings provide new insights into the energetic, physical, and conformational properties of GQs and expose subtle, but important, differences between DNA and RNA GQs with the same fold.
G-四链体（GQs）在DNA和RNA富含鸟嘌呤的序列中形成，产生高度稳定且结构多样的非经典核酸结构。GQs在调节转录、翻译和复制以及维持基因组等方面发挥着关键作用，因此其结构的改变会导致癌症等疾病。先前使用可极化分子动力学模拟的研究表明，尽管端粒GQs和TERRA GQs在结构上相似，但它们在离子结合特性方面存在差异。在这里，我们结合基于体积的元动力学和排斥势模拟以及可极化力场，来量化离子结合对GQ动力学和离子结合自由能的影响。此外，我们描述了GQs如何在其周围环境中施加电场，以将动力学与电子结构的变化联系起来。我们的研究结果为GQs的能量、物理和构象性质提供了新的见解，并揭示了具有相同折叠的DNA和RNA GQs之间细微但重要的差异。
