Evolution of Stronger SARS-CoV-2 Variants as Revealed Through the Lens of Molecular Dynamics Simulations.
Evolution of Stronger SARS-CoV-2 Variants as Revealed Through the Lens of Molecular Dynamics Simulations.
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DOI：
10.1007/s10930-022-10065-6
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发表时间：
2022-10
期刊：
影响因子：
3
通讯作者：
Bhattacharyya, Sudeep
中科院分区：
文献类型：
--
作者：
Wozney, Alec J.;Smith, Macey A.;Abdrabbo, Mobeen;Birch, Cole M.;Cicigoi, Kelsey A.;Dolan, Connor C.;Gerzema, Audrey E. L.;Hansen, Abby;Henseler, Ethan J.;LaBerge, Ben;Leavens, Caterra M.;Le, Christine N.;Lindquist, Allison C.;Ludwig, Rikaela K.;O'Reilly, Maggie G.;Reynolds, Jacob H.;Sherman, Brandon A.;Sillman, Hunter W.;Smith, Michael A.;Snortheim, Marissa J.;Svaren, Levi M.;Vanderpas, Emily C.;Voon, Aidan;Wackett, Miles J.;Weiss, Moriah M.;Hati, Sanchita;Bhattacharyya, Sudeep
使用分子动力学模拟，研究了野生型和严重急性呼吸综合征冠状病毒 2 刺突蛋白的七个变体的受体结合域和人血管紧张素转换酶 2 的肽酶域之间的蛋白质-蛋白质相互作用。这些变体是 alpha、beta、gamma、delta、eta、kappa 和 omicron。使用 100 ns 模拟数据，确定了蛋白质-蛋白质界面处的残基相互作用网络。此外，还研究了突变对模拟蛋白质-蛋白质复合物的基本蛋白质动力学、骨架灵活性和相互作用能的影响。野生型、δ 和 omicron 变体的蛋白质-蛋白质界面包含几种更强的相互作用，而 α、β、gamma、eta 和 kappa 变体则表现出相反的情况，从残基间相互作用距离和成对相互作用能量的分析中可以明显看出。研究表明，中央和右侧接触区域的两个不同的残基网络在蛋白质伴侣之间形成了更强的结合亲和力。该研究提供了分子水平的见解，了解 delta 和 omicron 变体增强的传播性和感染性最有可能与结合界面上的少数相互作用残基有关，这可能用于未来的抗体构建和基于结构的抗病毒药物设计。 在线版本包含可在 10.1007/s10930-022-10065-6 获取的补充材料。
Using molecular dynamics simulations, the protein–protein interactions of the receptor-binding domain of the wild-type and seven variants of the severe acute respiratory syndrome coronavirus 2 spike protein and the peptidase domain of human angiotensin-converting enzyme 2 were investigated. These variants are alpha, beta, gamma, delta, eta, kappa, and omicron. Using 100 ns simulation data, the residue interaction networks at the protein–protein interface were identified. Also, the impact of mutations on essential protein dynamics, backbone flexibility, and interaction energy of the simulated protein–protein complexes were studied. The protein–protein interface for the wild-type, delta, and omicron variants contained several stronger interactions, while the alpha, beta, gamma, eta, and kappa variants exhibited an opposite scenario as evident from the analysis of the inter-residue interaction distances and pair-wise interaction energies. The study reveals that two distinct residue networks at the central and right contact regions forge stronger binding affinity between the protein partners. The study provides a molecular-level insight into how enhanced transmissibility and infectivity by delta and omicron variants are most likely tied to a handful of interacting residues at the binding interface, which could potentially be utilized for future antibody constructs and structure-based antiviral drug design. The online version contains supplementary material available at 10.1007/s10930-022-10065-6.
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影响因子：
16.6
作者：
Koehler M;Ray A;Moreira RA;Juniku B;Poma AB;Alsteens D
通讯作者：
Alsteens D
基于计算机模拟快速评估 SARS-COV-2 刺突蛋白与人血管紧张素转换酶 2 受体和中和生物分子的结合亲和力
影响因子：
7.3
作者：
Buratto D;Saxena A;Ji Q;Yang G;Pantano S;Zonta F
通讯作者：
Zonta F
影响因子：
28.3
作者：
Gorbalenya, Alexander E.;Baker, Susan C.;Ziebuhr, John
通讯作者：
Ziebuhr, John
影响因子：
2.9
作者：
HOOVER, WG
通讯作者：
HOOVER, WG
影响因子：
3
作者：
BROOKS, BR;BRUCCOLERI, RE;KARPLUS, M
通讯作者：
KARPLUS, M