Rapid Assessment of Binding Affinity of SARS-COV-2 Spike Protein to the Human Angiotensin-Converting Enzyme 2 Receptor and to Neutralizing Biomolecules Based on Computer Simulations.
Rapid Assessment of Binding Affinity of SARS-COV-2 Spike Protein to the Human Angiotensin-Converting Enzyme 2 Receptor and to Neutralizing Biomolecules Based on Computer Simulations.
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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
DOI：
10.3389/fimmu.2021.730099
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发表时间：
2021
影响因子：
7.3
通讯作者：
Zonta F
中科院分区：
文献类型：
--
作者：
Buratto D;Saxena A;Ji Q;Yang G;Pantano S;Zonta F
SARS-CoV-2感染人类并导致2019冠状病毒病（COVID-19）。SARS-CoV-2的刺突糖蛋白的S1结构域通过其受体结合结构域与人血管紧张素转换酶2（hACE 2）结合，而S2结构域促进病毒与宿主细胞膜之间的融合以进入。流行的SARS-CoV-2基因组的刺突糖蛋白是一个突变热点。一些突变可能会影响hACE 2的结合亲和力，而另一些突变可能会调节S-糖蛋白的表达，或者它们可能会导致病毒能够逃脱原始变体感染或疫苗接种产生的抗体。由于大量变异正在出现，因此能够快速评估其特征至关重要：虽然结合亲和力的变化本身并不总是对病毒产生直接优势，但它们仍然可以提供关于进化压力方向的重要见解。在这里，我们提出了一个简单的和具有成本效益的计算协议的基础上分子动力学模拟，以快速筛选突变的刺突蛋白结合到hACE 2受体和选定的中和生物分子的能力。我们的研究结果表明，它是可能实现快速和可靠的预测结合亲和力。类似的方法可用于对S-RBD突变的潜在影响进行初步筛选，有助于优先考虑更耗时和昂贵的实验工作。
SARS-CoV-2 infects humans and causes Coronavirus disease 2019 (COVID-19). The S1 domain of the spike glycoprotein of SARS-CoV-2 binds to human angiotensin-converting enzyme 2 (hACE2) via its receptor-binding domain, while the S2 domain facilitates fusion between the virus and the host cell membrane for entry. The spike glycoprotein of circulating SARS-CoV-2 genomes is a mutation hotspot. Some mutations may affect the binding affinity for hACE2, while others may modulate S-glycoprotein expression, or they could result in a virus that can escape from antibodies generated by infection with the original variant or by vaccination. Since a large number of variants are emerging, it is of vital importance to be able to rapidly assess their characteristics: while changes of binding affinity alone do not always cause direct advantages for the virus, they still can provide important insights on where the evolutionary pressure is directed. Here, we propose a simple and cost-effective computational protocol based on Molecular Dynamics simulations to rapidly screen the ability of mutated spike protein to bind to the hACE2 receptor and selected neutralizing biomolecules. Our results show that it is possible to achieve rapid and reliable predictions of binding affinities. A similar approach can be used to perform preliminary screenings of the potential effects of S-RBD mutations, helping to prioritize the more time-consuming and expensive experimental work.
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影响因子：
5.9
作者：
Bolles, Meagan;Donaldson, Eric;Baric, Ralph
通讯作者：
Baric, Ralph
影响因子：
3
作者：
Pettersen, EF;Goddard, TD;Ferrin, TE
通讯作者：
Ferrin, TE
影响因子：
5.6
作者：
Cournia, Zoe;Allen, Bryce;Sherman, Woody
通讯作者：
Sherman, Woody
影响因子：
56.9
作者：
Chandrashekar, Abishek;Liu, Jinyan;Barouch, Dan H.
通讯作者：
Barouch, Dan H.
皮摩尔SARS-COV-2小蛋白抑制剂的从头设计。
DOI：
10.1126/science.abd9909
发表时间：
2020-10-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cao L;Goreshnik I;Coventry B;Case JB;Miller L;Kozodoy L;Chen RE;Carter L;Walls AC;Park YJ;Strauch EM;Stewart L;Diamond MS;Veesler D;Baker D
通讯作者：
Baker D