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arXiv · 2103.00399

Hydrophobic interaction determines docking affinity of SARS CoV 2 variants with antibodies

Jiacheng Li·Chengyu Hou·Menghao Wang·Chencheng Liao·Shuai Guo·Liping Shi·Xiaoliang Ma·Hongchi Zhang·Shenda Jiang·Bing Zheng·Lin Ye·Lin Yang·Xiaodong He
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Abstract

Preliminary epidemiologic, phylogenetic and clinical findings suggest that several novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have increased transmissibility and decreased efficacy of several existing vaccines. Four mutations in the receptor-binding domain (RBD) of the spike protein that are reported to contribute to increased transmission. Understanding physical mechanism responsible for the affinity enhancement between the SARS-CoV-2 variants and ACE2 is the "urgent challenge" for developing blockers, vaccines and therapeutic antibodies against the coronavirus disease 2019 (COVID-19) pandemic. Based on a hydrophobic-interaction-based protein docking mechanism, this study reveals that the mutation N501Y obviously increased the hydrophobic attraction and decrease hydrophilic repulsion between the RBD and ACE2 that most likely caused the transmissibility increment of the variants. By analyzing the mutation-induced hydrophobic surface changes in the attraction and repulsion at the binding site of the complexes of the SARS-CoV-2 variants and antibodies, we found out that all the mutations of N501Y, E484K, K417N and L452R can selectively decrease or increase their binding affinity with some antibodies.

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Jiacheng Li, Chengyu Hou, Menghao Wang, Chencheng Liao, Shuai Guo, Liping Shi, Xiaoliang Ma, Hongchi Zhang, Shenda Jiang, Bing Zheng, Lin Ye, Lin Yang, Xiaodong He. 2021-02-28. Hydrophobic interaction determines docking affinity of SARS CoV 2 variants with antibodies. https://arxiv.org/abs/2103.00399

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