2019年底,一种新型冠状病毒的出现导致其被鉴定为SARS-CoV-2,从而加速了COVID-19大流行的爆发。对SARS-CoV-2进行了许多实验和计算研究,以了解其行为和模式。在这项研究中,分子动力学(MD)模拟用于比较SARS-CoV-2及其关注变体(VOC)-Alpha的行为,Beta,Gamma,Delta,和Omicron-与hACE2蛋白。对来自蛋白质数据库(PDB)的蛋白质结构进行比对,并使用嵌合体进行修整,专注于负责ACE2相互作用的受体结合域(RBD)。使用视觉分子动力学(VMD)和纳米级分子动力学(NAMD2)进行MD模拟,从这些模拟结果中提取了盐桥和氢键数据。从10ns模拟的最后5ns中提取的数据被可视化,提供对每个变体与ACE2相互作用的相对稳定性的见解。此外,计算了静电和疏水性蛋白质表面,可视化,并分析。我们全面的计算结果有助于药物发现和未来的疫苗设计,因为它们提供了有关蛋白质-蛋白质相互作用(PPI)中重要氨基酸的信息。我们的分析表明,原始和Omicron变体是两种结构上最相似的蛋白质。γ变体通过氢键与hACE2形成最强的相互作用,而Alpha和Delta形成最稳定的盐桥;Omicron由结合位点的正电势主导,这使得吸引hACE2受体变得容易;同时,原始的,Beta,Delta,和Omicron变体通过氢键和盐桥显示出不同水平的相互作用稳定性,这表明靶向治疗剂可以破坏这些关键的相互作用以预防SARS-CoV-2感染。
In late 2019, the emergence of a novel coronavirus led to its identification as SARS-CoV-2, precipitating the onset of the COVID-19 pandemic. Many experimental and computational studies were performed on SARS-CoV-2 to understand its behavior and patterns. In this research, Molecular Dynamic (MD) simulation is utilized to compare the behaviors of SARS-CoV-2 and its Variants of Concern (VOC)-Alpha, Beta, Gamma, Delta, and Omicron-with the hACE2 protein. Protein structures from the Protein Data Bank (PDB) were aligned and trimmed for consistency using Chimera, focusing on the receptor-binding domain (RBD) responsible for ACE2 interaction. MD simulations were performed using Visual Molecular Dynamics (VMD) and Nanoscale Molecular Dynamics (NAMD2), and salt bridges and hydrogen bond data were extracted from the results of these simulations. The data extracted from the last 5 ns of the 10 ns simulations were visualized, providing insights into the comparative stability of each variant\'s interaction with ACE2. Moreover, electrostatics and hydrophobic protein surfaces were calculated, visualized, and analyzed. Our comprehensive computational results are helpful for drug discovery and future vaccine designs as they provide information regarding the vital amino acids in protein-protein interactions (PPIs). Our analysis reveals that the Original and Omicron variants are the two most structurally similar proteins. The Gamma variant forms the strongest interaction with hACE2 through hydrogen bonds, while Alpha and Delta form the most stable salt bridges; the Omicron is dominated by positive potential in the binding site, which makes it easy to attract the hACE2 receptor; meanwhile, the Original, Beta, Delta, and Omicron variants show varying levels of interaction stability through both hydrogen bonds and salt bridges, indicating that targeted therapeutic agents can disrupt these critical interactions to prevent SARS-CoV-2 infection.