Deniz Tekin E
Computer Engineering Department, University of Turkish Aeronautical Association, Ankara 06990, Turkey.
Comput Theor Chem. 2023 Apr;1222:114049. doi: 10.1016/j.comptc.2023.114049. Epub 2023 Feb 1.
A lot of effort has been made in developing vaccine and therapeutic agents against the SARS-CoV-2, concentrating on the Spike protein that binds angiotensin-converting enzyme 2 on human cells. Nowadays, some researches study the role of the -linked glycans as potential targets for vaccines and new agents. Due to the flexibility and diversity of the -linked glycans, in this work, we focus on the -Acetylglucosamine moiety, which is the precursor of nearly all eukaryotic glycans. We performed molecular dynamics simulations to study the effects of the -Acetylglucosamine on the stability of the spike glycoprotein in SARS-CoV-2. After a 100 ns of simulation on the spike proteins without and with the -Acetylglucosamine molecules, we found that the presence of -Acetylglucosamine increases the local stability in their vicinity; even though their effect on the full structure is negligible. Thus; it can be inferred that the -Acetylglucosamine moieties can potentially affect the interaction of the S protein with the ACE2 receptor. We also found that the S1 domain is more flexible than the S2 domain. We propose which of the experimentally observed glycans found on the spike may be more functional than the others. Detailed understanding of glycans is key for the development of new therapeutic strategies.
在开发针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的疫苗和治疗药物方面已经付出了很多努力，重点集中在与人类细胞上的血管紧张素转换酶2结合的刺突蛋白上。如今，一些研究将N-连接聚糖的作用作为疫苗和新药物的潜在靶点进行研究。由于N-连接聚糖的灵活性和多样性，在这项工作中，我们专注于N-乙酰葡糖胺部分，它是几乎所有真核生物聚糖的前体。我们进行了分子动力学模拟，以研究N-乙酰葡糖胺对SARS-CoV-2刺突糖蛋白稳定性的影响。在对不含和含有N-乙酰葡糖胺分子的刺突蛋白进行100纳秒的模拟后，我们发现N-乙酰葡糖胺的存在增加了其附近区域的局部稳定性；尽管它们对整个结构的影响可以忽略不计。因此，可以推断N-乙酰葡糖胺部分可能会影响S蛋白与ACE2受体的相互作用。我们还发现S1结构域比S2结构域更具灵活性。我们提出在刺突上实验观察到的哪些聚糖可能比其他聚糖更具功能性。对聚糖的详细了解是开发新治疗策略的关键。
