Solvent-Modulated Energetics of Tetrameric DNA Polymorphism

四聚体 DNA 多态性的溶剂调节能量学

• 批准号: RGPIN-2017-06574
• 负责人: Chalikian, Tigran
• 金额: $ 2.04万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=632543
• 关键词: Solvent; Modulated; Energetics; Tetrameric; DNA

We propose to continue our studies to characterize the thermodynamic content of the role of solvent in modulating the binding affinity and conformational preferences of biopolymers. During the previous budget period, our studies were focussed on investigating the role of water and water-soluble cosolvents in the energetics of protein and nucleic acid transitions and ligand-protein binding. In parallel, we have begun to establish a program in which we characterize the influence of solvent and individual solvent components on the energetics of DNA G-quadruplexes and i-motifs. G-quadruplexes and i-motifs form an important class of noncanonical tetrameric DNA structures of biological importance. Guanine-rich DNA strands are prone to fold into various G-quadruplex structures in which guanine bases associate with each other in stable hydrogen-bonded arrangements, G-quartets. Cytosine-rich strands exhibit a propensity to fold into the i-motif conformation at slightly acidic to near neutral pH. The latter represents a DNA conformation with a tetraplex arrangement of two parallel-stranded duplexes intercalated into each other in an antiparallel orientation.

我们建议继续我们的研究，以表征溶剂在调节生物聚合物的结合亲和力和构象偏好的作用的热力学内容。在上一个预算期间，我们的研究重点是调查水和水溶性共溶剂在蛋白质和核酸转换以及配体-蛋白质结合的能量学中的作用。与此同时，我们已经开始建立一个程序，在该程序中，我们表征溶剂和单个溶剂组分对DNA G-四链体和i-基序的能量学的影响。G-四链体和i-基序形成一类重要的具有生物学重要性的非规范四聚体DNA结构。富含鸟嘌呤的DNA链易于折叠成各种G-四链体结构，其中鸟嘌呤碱基以稳定的氢键排列彼此缔合，即G-四联体。富含胞嘧啶的链表现出在弱酸性至接近中性pH下折叠成i-基序构象的倾向。后者代表具有两个平行链双链体以反平行方向插入彼此的四链体排列的DNA构象。