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The glycan‐mediated mechanism on the interactions of gp120 with CD 4 and antibody: Insights from molecular dynamics simulation
Author(s) -
Zhang Yan,
Niu Yuzhen,
Tian Jiaqi,
Liu Xuewei,
Yao Xiaojun,
Liu Huanxiang
Publication year - 2017
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13045
Subject(s) - glycan , antibody , neutralization , chemistry , biology , biochemistry , glycoprotein , immunology
N‐linked glycans such as 234 and 276 gp 120 glycans are vital components of HIV evasion from humoral immunity and important for HIV ‐1 neutralization of many broadly neutralizing antibodies ( bNA bs). However, it is unknown the action mechanism of two glycans. To investigate the roles of the glycans on the interactions of gp120 with CD 4 and antibody, molecular dynamic simulations based on gp120‐ CD 4‐8 ANC 195 complex with 234 and 276 gp 120 glycans, 234 gp 120 glycan, 276 gp 120 glycan, and without glycan were performed. Our results reveal that 276 gp 120 glycan can enhance gp120‐ CD 4 and gp120‐antibody interactions through the formation of hydrogen bonds of the glycan with CD 4 and antibody and make the binding interface of gp120, CD 4 and antibody stable; 234 gp 120 glycan primarily reinforces gp120‐antibody interactions and weakly affects gp120‐ CD 4 interactions as it mainly lies between gp120 and antibody. The co‐operating of two glycans can enhance gp120‐ CD 4 and gp120‐antibody associations. Through the structural analysis, it can be seen that 234 gp 120 glycan leads to moving upward of two glycans and the variable region of heavy chain, which is favorable for the interactions of gp120 with CD 4 and antibody. The information obtained in this study can provide the guidance for design vaccines and small molecule inhibitors.