Omicron BA.1 and BA.2 variants increase the interactions of SARS-CoV-2 spike glycoprotein with ACE2.
Omicron BA.1 and BA.2 variants increase the interactions of SARS-CoV-2 spike glycoprotein with ACE2.
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DOI：
10.1016/j.jmgm.2022.108286
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发表时间：
2022-12
影响因子：
2.9
通讯作者：
Gur, Mert
中科院分区：
文献类型：
--
作者：
Golcuk, Mert;Yildiz, Ahmet;Gur, Mert
SARS-CoV-2感染是通过其刺突糖蛋白的受体结合结构域（RBD）与宿主细胞中血管紧张素转换酶2（ACE 2）受体的肽酶结构域（PD）结合而启动的。最近检测到的SARS-CoV-2的Omicron变体（B.1.1.529）在RBD上发生了严重突变。首先是BA.1和后来的BA.2变体成为Omicron变体的最主要菌株。为了研究这些菌株的突变如何影响RBD-PD相互作用，我们在存在全长聚糖、明确的水和离子的情况下对BA.1和BA.2 RBD-PD进行了全原子分子动力学模拟。模拟结果显示，与野生型RBD相比，BA.1和BA.2变体的RBD表现出更分散的相互作用网络，并与PD形成更多的盐桥和疏水相互作用。尽管BA.1和BA.2在RBD-ACE 2界面处的两个残基不同，但在这些变体之间未观察到RBD-PD相互作用和结合强度的重大差异。使用在每个轨迹中采样的构象，分子力学泊松-玻尔兹曼表面积（MMPBSA）方法估计BA.1和BA.2 RBD与PD的结合自由能分别比野生型RBD强34%和51%，这可能导致Omicron变体感染宿主细胞的结合效率更高。
SARS-CoV-2 infection is initiated by binding of the receptor-binding domain (RBD) of its spike glycoprotein to the peptidase domain (PD) of angiotensin-converting enzyme 2 (ACE2) receptors in host cells. Recently detected Omicron variant of SARS-CoV-2 (B.1.1.529) is heavily mutated on RBD. First the BA.1 and later the BA.2 variant became the most dominant strains of the Omicron variant. To investigate how the mutations of these strains affect RBD-PD interactions, we performed all-atom molecular dynamics simulations of the BA.1 and BA.2 RBD-PD in the presence of full-length glycans, explicit water, and ions. Simulations revealed that RBDs of BA.1 and BA.2 variants exhibit a more dispersed interaction network and make an increased number of salt bridges and hydrophobic interactions with PD compared to wild-type RBD. Although BA.1 and BA.2 differ in two residues at the RBD-ACE2 interface, no major difference in RBD-PD interactions and binding strengths were observed between these variants. Using the conformations sampled in each trajectory, the Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) method estimated ∼34% and ∼51% stronger binding free energies to PD for BA.1 and BA.2 RBD, respectively, than wild-type RBD, which may result in higher binding efficiency of the Omicron variant to infect host cells.
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影响因子：
64.8
作者：
Barnes CO;Jette CA;Abernathy ME;Dam KA;Esswein SR;Gristick HB;Malyutin AG;Sharaf NG;Huey-Tubman KE;Lee YE;Robbiani DF;Nussenzweig MC;West AP Jr;Bjorkman PJ
通讯作者：
Bjorkman PJ
超越屏蔽：聚糖在SARS-COV-2尖峰蛋白中的作用。
影响因子：
18.2
作者：
Casalino L;Gaieb Z;Goldsmith JA;Hjorth CK;Dommer AC;Harbison AM;Fogarty CA;Barros EP;Taylor BC;McLellan JS;Fadda E;Amaro RE
通讯作者：
Amaro RE
影响因子：
5.6
作者：
Golcuk, Mert;Hacisuleyman, Aysima;Yilmaz, Sema Zeynep;Taka, Elhan;Yildiz, Ahmet;Gur, Mert
通讯作者：
Gur, Mert
影响因子：
56.9
作者：
McCallum, Matthew;Czudnochowski, Nadine;Rosen, Laura E.;Zepeda, Samantha K.;Bowen, John E.;Walls, Alexandra C.;Hauser, Kevin;Joshi, Anshu;Stewart, Cameron;Dillen, Josh R.;Powell, Abigail E.;Croll, Tristan, I;Nix, Jay;Virgin, Herbert W.;Corti, Davide;Snell, Gyorgy;Veesler, David
通讯作者：
Veesler, David
CaFE：使用终点自由能方法进行结合亲和力预测的工具
影响因子：
5.8
作者：
Liu, Hui;Hou, Tingjun
通讯作者：
Hou, Tingjun