KU Leuven, Rega Institute for Medical Research, Medicinal Chemistry, Herestraat 49 - Box 1041, 3000 Leuven, Belgium.
Campus Drie Eiken, Laboratory of Medicinal Chemistry, UAntwerp, Universiteitsplein 1, B-2610 Wilrijk, Belgium.
J Chem Theory Comput. 2021 Jun 8;17(6):3814-3823. doi: 10.1021/acs.jctc.1c00270. Epub 2021 May 17.
Puckering of the sugar unit in nucleosides and nucleotides is an important structural aspect that directly influences the helical structure of nucleic acids. The preference for specific puckering modes in nucleic acids can be analyzed via conformational analysis, but the large amount of conformations and the accuracy of the analysis leads to an extensive amount of computational time. In this paper, we show that the combination of geometry optimizations with the HF-3c method with single point energies at the RI-MP2 level results in accurate results for the puckering potential energy surface (PES) of DNA and RNA nucleosides while significantly reducing the necessary computational time. Applying this method to a series of known xeno nucleic acids (XNAs) allowed us to rapidly explore the puckering PES of each of the respective nucleosides and to explore the puckering PES of six-membered modified XNA (HNA and β-homo-DNA) for the first time.
糖单位在核苷和核苷酸中的卷曲是一个重要的结构方面，直接影响核酸的螺旋结构。可以通过构象分析来分析核酸中特定卷曲模式的偏好，但大量的构象和分析的准确性导致计算时间的大量增加。在本文中，我们表明，将几何优化与 HF-3c 方法与 RI-MP2 水平的单点能相结合，可以得到 DNA 和 RNA 核苷的卷曲势能面 (PES) 的准确结果，同时大大减少了所需的计算时间。将该方法应用于一系列已知的异核酸 (XNAs)，使我们能够快速探索每个核苷的卷曲 PES，并首次探索六元修饰 XNA (HNA 和 β-同型-DNA) 的卷曲 PES。
