论文标题
比较SARS-COV-2和SARS-COV的受体结合结构域中的结合相互作用
Comparing the binding interactions in the receptor binding domains of SARS-CoV-2 and SARS-CoV
论文作者
论文摘要
Covid-19自从中国武汉出现以来，由于其高感染率一直是一个主要问题，在世界各地留下了超过一百万感染的人。与SARS-COV-1相比，大量研究试图揭示SARS-COV-2的结构，以抑制这种高感染率。其中一些研究表明，SARS-COV-1尖峰蛋白中的突变可能是其对ACE2人类细胞受体的较高亲和力的原因。在这项工作中，我们使用了分子动力学模拟和蒙特卡洛采样来比较SARS-COV和SARS-COV-2的尖峰蛋白与ACE2的结合亲和力。我们发现，由于静电相互作用的增强，SARS-COV-2通过7 kcal/mol与SARS-COV更强的ACE2结合。静电结合能的主要贡献是由SARS-COV和K417和SARS-COV2的R426和ACE2-E329之间形成的盐桥产生的。另外，单个突变体对结合能没有显着贡献。然而，这些突变引起了复杂的结构变化，从而增强了结合能。我们的结果还表明，SARS-COV-2不太可能是实验室工程病毒。
COVID-19, since emerged in Wuhan, China, has been a major concern due to its high infection rate, leaving more than one million infected people around the world. Huge number of studies tried to reveal the structure of the SARS-CoV-2 compared to the SARS-CoV-1, in order to suppress this high infection rate. Some of these studies showed that the mutations in the SARS-CoV-1 Spike protein might be responsible for its higher affinity to the ACE2 human cell receptor. In this work, we used molecular dynamics simulations and Monte Carlo sampling to compare the binding affinities of the spike proteins of SARS-CoV and SARS-CoV-2 to the ACE2. We found that the SARS-CoV-2 binds to ACE2 stronger than SARS-CoV by 7 kcal/mol, due to enhanced electrostatic interactions. The major contributions to the electrostatic binding energies are resulting from the salt-bridges formed between R426 and ACE2-E329 in case of SARS-CoV and K417 and ACE2-D30 for SARS-CoV2. In addition, there is no significant contribution from a single mutant to the binding energies. However, these mutations induce sophisticated structural changes that enhance the binding energies. Our results also indicate that the SARS-CoV-2 is unlikely a lab engineered virus.
