Remdesivir(RDV)是对抗SARS-CoV-2病毒大流行的有效药物。RDV作用机制中的关键步骤之一是将其掺入正在生长的RNA链中。RDV,一种腺苷类似物,与尿苷在互补链中形成Watson-Crick(WC)型氢键,这种相互作用的强度将控制RDV的功效。虽然有大量关于天然碱基对中WCH键的结构和能量信息,尚未在原子水平上研究RDV与尿苷的相互作用。在这篇文章中,我们的目标是弥合这个差距,为了理解RDV及其氢键相互作用,通过在M06-2X/cc-pVDZ水平下采用密度泛函理论(DFT)。相互作用的能量,QTAIM分析,对RDV执行NBO和SAPT2,腺苷,以及它们与尿苷的复合物,以深入了解氢键的性质。计算表明RDV具有相似的几何形状,精力充沛,分子轨道,和芳香作为腺苷,表明RDV是一种有效的腺苷类似物。重要的几何参数,例如腺苷拉伸振动模式中的键距离和红移,RDV和尿苷识别两个WC型H键。使用QTAIM参数和计算的氢键能计算这两个H键的相对强度。最后,SAPT2研究在最小值和非平衡碱基对距离下进行,以了解主要的分子间物理力。这项研究,基于对各种计算的全面分析,表明腺苷和RDV具有相似的结构,精力充沛,和氢键行为。
Remdesivir (RDV) emerged as an effective drug against the SARS-CoV-2 virus pandemic. One of the crucial steps in the mechanism of action of RDV is its incorporation into the growing RNA strand. RDV, an adenosine analogue, forms Watson-Crick (WC) type hydrogen bonds with uridine in the complementary strand and the strength of this interaction will control efficacy of RDV. While there is a plethora of structural and energetic information available about WC H-bonds in natural base pairs, the interaction of RDV with uridine has not been studied yet at the atomic level. In this article, we aim to bridge this gap, to understand RDV and its hydrogen bonding interactions, by employing density functional theory (DFT) at the M06-2X/cc-pVDZ level. The interaction energy, QTAIM analysis, NBO and SAPT2 are performed for RDV, adenosine, and their complex with uridine to gain insights into the nature of hydrogen bonding. The computations show that RDV has similar geometry, energetic, molecular orbitals, and aromaticity as adenosine, suggesting that RDV is an effective adenosine analogue. The important geometrical parameters, such as bond distances and red-shift in the stretching vibrational modes of adenosine, RDV and uridine identify two WC-type H-bonds. The relative strength of these two H-bonds is computed using QTAIM parameters and the computed hydrogen bond energy. Finally, the SAPT2 study is performed at the minima and at non-equilibrium base pair distances to understand the dominant intermolecular physical force. This study, based on a thorough analysis of a variety of computations, suggests that both adenosine and RDV have similar structure, energetic, and hydrogen bonding behaviour.