The glycan-mediated mechanism on the interactions of gp120 with CD4 and antibody: Insights from molecular dynamics simulation

Yan Zhang, Yuzhen Niu, Jiaqi Tian, Xuewei Liu, Xiaojun Yao, Huanxiang Liu

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1237-1246
Number of pages10
JournalChemical Biology and Drug Design
Volume90
Issue number6
DOIs
Publication statusPublished - Dec 2017
Externally publishedYes

Keywords

  • 8ANC195
  • CD4
  • HIV-1
  • gp120
  • molecular dynamics simulation

Fingerprint

Dive into the research topics of 'The glycan-mediated mechanism on the interactions of gp120 with CD4 and antibody: Insights from molecular dynamics simulation'. Together they form a unique fingerprint.

Cite this