The glycan‐mediated mechanism on the interactions of gp120 with CD4 and antibody: Insights from molecular dynamics simulation
The glycan‐mediated mechanism on the interactions of gp120 with CD4 and antibody: Insights from molecular dynamics simulation
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DOI：
10.1111/cbdd.13045
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发表时间：
2017-12
影响因子：
3
通讯作者：
Yan Zhang;Yuzhen Niu;Jiaqi Tian;Xuewei Liu;X. Yao;Huanxiang Liu
中科院分区：
文献类型：
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作者：
Yan Zhang;Yuzhen Niu;Jiaqi Tian;Xuewei Liu;X. Yao;Huanxiang Liu
N 连接聚糖（例如 234 和 276 gp120 聚糖）是 HIV 逃避体液免疫的重要组成部分，对于许多广泛中和抗体 (bNAb) 的 HIV-1 中和也很重要。然而，两种聚糖的作用机制尚不清楚。为了研究聚糖对 gp120 与 CD4 和抗体相互作用的作用，进行了基于 gp120-CD4-8ANC195 复合物与 234 和 276 gp120 聚糖、234 gp120 聚糖、276 gp120 聚糖和无聚糖的分子动力学模拟。我们的结果表明，276 gp120聚糖可以通过聚糖与CD4和抗体形成氢键来增强gp120-CD4和gp120-抗体相互作用，并使gp120、CD4和抗体的结合界面稳定； 234 gp120 聚糖主要增强 gp120-抗体相互作用，对 gp120-CD4 相互作用影响较弱，因为它主要位于 gp120 和抗体之间。两个聚糖的协同作用可以增强 gp120-CD4 和 gp120-抗体的结合。通过结构分析可以看出，234个gp120聚糖导致两个聚糖和重链可变区向上移动，有利于gp120与CD4和抗体的相互作用。本研究获得的信息可以为设计疫苗和小分子抑制剂提供指导。
N‐linked glycans such as 234 and 276 gp120 glycans are vital components of HIV evasion from humoral immunity and important for HIV‐1 neutralization of many broadly neutralizing antibodies (bNAbs). However, it is unknown the action mechanism of two glycans. To investigate the roles of the glycans on the interactions of gp120 with CD4 and antibody, molecular dynamic simulations based on gp120‐CD4‐8ANC195 complex with 234 and 276 gp120 glycans, 234 gp120 glycan, 276 gp120 glycan, and without glycan were performed. Our results reveal that 276 gp120 glycan can enhance gp120‐CD4 and gp120‐antibody interactions through the formation of hydrogen bonds of the glycan with CD4 and antibody and make the binding interface of gp120, CD4 and antibody stable; 234 gp120 glycan primarily reinforces gp120‐antibody interactions and weakly affects gp120‐CD4 interactions as it mainly lies between gp120 and antibody. The co‐operating of two glycans can enhance gp120‐CD4 and gp120‐antibody associations. Through the structural analysis, it can be seen that 234 gp120 glycan leads to moving upward of two glycans and the variable region of heavy chain, which is favorable for the interactions of gp120 with CD4 and antibody. The information obtained in this study can provide the guidance for design vaccines and small molecule inhibitors.