The new SARS-CoV-2 strain shows a stronger binding affinity to ACE2 due to N501Y mutant.
The new SARS-CoV-2 strain shows a stronger binding affinity to ACE2 due to N501Y mutant.
复制标题
由于N501Y突变，新的SARS-CoV-2毒株与ACE2具有更强的结合亲和力。
DOI：
10.1016/j.medidd.2021.100086
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发表时间：
2021-06
影响因子：
--
通讯作者：
Amin M
中科院分区：
文献类型：
--
作者：
Ali F;Kasry A;Amin M
SARS-CoV-2是一个全球性的挑战，因为它的传播能力比SARS-CoV快得多，这归因于受体结合结构域（RBD）的突变。这些突变增强了静电相互作用。最近，英国报道了一种新的菌株，其中包括RBD中的突变（N501 Y），这可能会增加感染率。在这里，使用分子动力学模拟（MD）和蒙特卡罗（MC）采样，我们表明，N501突变增强了静电相互作用，由于SARS-CoV-2-T500和ACE 2-D355之间形成了强氢键附近的突变位点。另外，我们观察到SARS-CoV-2野生型和突变型与ACE 2之间的静电相互作用主要是由SARS-CoV-2-K417与ACE 2-D30、SARS-CoV-2-K458、ACE 2-E23、SARS-CoV-2-R403与ACE 2-E37之间形成的盐桥所主导。这些相互作用贡献了总结合能的40%以上。
SARS-CoV-2 is a global challenge due to its ability to spread much faster than the SARS-CoV, which was attributed to the mutations in the receptor binding domain (RBD). These mutations enhanced the electrostatic interactions. Recently, a new strain is reported in the UK that includes a mutation (N501Y) in the RBD, that is possibly increasing the infection rate. Here, using Molecular Dynamics simulations (MD) and Monte Carlo (MC) sampling, we show that the N501 mutation enhanced the electrostatic interactions due to the formation of a strong hydrogen bond between SARS-CoV-2-T500 and ACE2-D355 near the mutation site. In addition, we observed that the electrostatic interactions between the SARS-CoV-2 and ACE2 in the wild type and the mutant are dominated by salt-bridges formed between SARS-CoV-2-K417 and ACE2-D30, SARS-CoV-2-K458, ACE2-E23, and SARS-CoV-2-R403 and ACE2-E37. These interactions contributed more than 40% of the total binding energies.