Akinwumi Ishola Abeeb, Bheemireddy Sneha, Chaloin Laurent, Perez Serge, Khakzad Hamed, Maigret Bernard, Karami Yasaman
Université de Lorraine, CNRS, Inria, LORIA, F-54000 Nancy, France.
Institut de Recherche en Infectiologie de Montpellier (IRIM), CNRS, Univ. Montpellier, 34293 Montpellier, France.
Comput Struct Biotechnol J. 2025 Jul 24;27:3285-3291. doi: 10.1016/j.csbj.2025.07.034. eCollection 2025.
The SARS-CoV-2 spike protein binds to the angiotensin-converting enzyme 2 (ACE2) receptor to mediate viral entry, with mutations in different variants influencing binding affinity and conformational dynamics. Using large-scale molecular dynamics simulations, we analyzed the Spike-ACE2 complex in the wild-type (WT), Beta, and Delta variants. Our findings reveal significant conformational rearrangements at the interface in Beta and Delta compared to WT, leading to distinct interaction networks and changes in complex stability. Binding free energy analysis further highlights variant-specific differences in ACE2 affinity, with alternative binding modes emerging over the simulation. The results enhance our understanding of spike-ACE2 stoichiometry across variants, providing implications for viral infectivity and therapeutic targeting.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突蛋白与血管紧张素转换酶2（ACE2）受体结合以介导病毒进入，不同变体中的突变会影响结合亲和力和构象动力学。我们使用大规模分子动力学模拟，分析了野生型（WT）、β和δ变体中的刺突-ACE2复合物。我们的研究结果表明，与野生型相比，β和δ变体界面处存在显著的构象重排，导致不同的相互作用网络和复合物稳定性变化。结合自由能分析进一步突出了ACE2亲和力的变体特异性差异，在模拟过程中出现了替代结合模式。这些结果加深了我们对不同变体刺突-ACE2化学计量的理解，为病毒感染性和治疗靶点提供了启示。
