Life Science Lab, Institute for Computational Science and Technology, Quang Trung Software City, Tan Chanh Hiep Ward, District 12, 729110 Ho Chi Minh City, Vietnam.
Faculty of Physics and Engineering Physics, VNUHCM-University of Science, 227, Nguyen Van Cu Street, District 5, 749000 Ho Chi Minh City, Vietnam.
J Chem Phys. 2024 Feb 7;160(5). doi: 10.1063/5.0188053.
The binding of the receptor binding domain (RBD) of the SARS-CoV-2 spike protein to the host cell receptor angiotensin-converting enzyme 2 (ACE2) is the first step in human viral infection. Therefore, understanding the mechanism of interaction between RBD and ACE2 at the molecular level is critical for the prevention of COVID-19, as more variants of concern, such as Omicron, appear. Recently, atomic force microscopy has been applied to characterize the free energy landscape of the RBD-ACE2 complex, including estimation of the distance between the transition state and the bound state, xu. Here, using a coarse-grained model and replica-exchange umbrella sampling, we studied the free energy landscape of both the wild type and Omicron subvariants BA.1 and XBB.1.5 interacting with ACE2. In agreement with experiment, we find that the wild type and Omicron subvariants have similar xu values, but Omicron binds ACE2 more strongly than the wild type, having a lower dissociation constant KD.
SARS-CoV-2 刺突蛋白的受体结合域（RBD）与宿主细胞受体血管紧张素转化酶 2（ACE2）的结合是病毒感染人体的第一步。因此，了解 RBD 和 ACE2 之间在分子水平上的相互作用机制对于预防 COVID-19 至关重要，因为越来越多的关注变体，如奥密克戎变体，不断出现。最近，原子力显微镜已被用于表征 RBD-ACE2 复合物的自由能景观，包括估计过渡态和结合态之间的距离，xu。在这里，我们使用粗粒模型和 replica-exchange 伞状采样研究了与 ACE2 相互作用的野生型和奥密克戎亚变种 BA.1 和 XBB.1.5 的自由能景观。与实验结果一致，我们发现野生型和奥密克戎亚变种的 xu 值相似，但奥密克戎与 ACE2 的结合更强，解离常数 KD 更低。
