论文标题
SARS-COV-2感染中的尖峰构象转变
Spike conformation transition in SARS-CoV-2 infection
论文作者
论文摘要
提出了关于SARS-COV-2峰值蛋白构象转变的理论。从第一原则研究了尖峰的受体结合结构域（RBD）之间的构象平衡。构象状态种群是从S蛋白构象转变中的自由能变化推导的。我们证明了自由能包括两个部分，一个来自多构象潜力的多米尼马，另一部分来自结构弹性的变化。这两个因素都取决于氨基酸突变。前者与RBD对ACE 2的亲和力的变化有关，因为RBD的亚域RBM（受体结合基序）的突变。后者是由S蛋白弹性能量的变化引起的。当亲和力显着增加和/或弹性能量已大大降低时，平衡偏向开放构象。只有这样，病毒感染过程才能继续。预计将在RBD界面上5-9个位点的氨基酸突变中可能的新SARS-COV-2变体。构象转变所需的弹性能量变化是定量估计的。考虑到更多病毒变体的弹性结构变化是可能的。 D614G突变，K986p突变和当前SARS-COV-2大流行中的新变体501Y均可从提出的理论中解释。 SARS-COV-2与SARS-COV-1的感染性比较是从构象平衡点进行的。为什么病毒进入在较低温度和较高的湿度中被当前理论解释。还简要讨论了受电磁场影响的构象转变。
A theory on the conformation transition for SARS-CoV-2 spike protein (S) is proposed. The conformation equilibrium between open (up) and closed (down) conformations of receptor binding domain (RBD) of the spike is studied from the first-principle. The conformational state population is deduced from the free energy change in conformation transition of S protein. We demonstrated that the free energy includes two parts, one from the multi-minima of conformational potential and another from the variation of structural elasticity. Both factors are dependent of amino acid mutation. The former is related to the change of affinity of RBD to ACE 2 due to the mutation in the subdomain RBM (receptor binding motif) of RBD. The latter is caused by the change of elastic energy of S protein. When the affinity has increased significantly and/or the elastic energy has been reduced substantially the equilibrium is biased to the open conformation. Only then can the virus infection process continue. Possible new SARS-CoV-2 variants from amino acid mutations in 5-9 sites on RBD interface are predicted. The elastic energy variation needed for conformation transition is estimated quantitatively. Taking the elastic-structural change into account more virus variants are possible. Both the D614G mutation, the K986P mutation and the new variants 501Y in current SARS-CoV-2 pandemic can be interpreted from the presented theory. The comparison of the infectivity of SARS-CoV-2 with SARS-CoV-1 is made from the point of conformation equilibrium. Why the virus entrance takes priority in lower temperature and higher humidity is interpreted by the present theory. The conformational transition influenced by electromagnetic field is also discussed briefly.
