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The molecular mechanism of two coreceptor binding site antibodies X5 and 17b neutralizing HIV ‐1: Insights from molecular dynamics simulation
Author(s) -
Zhang Yan,
Guo Jingjing,
Huang Le,
Tian Jiaqi,
Yao Xiaojun,
Liu Huanxiang
Publication year - 2018
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.13201
Subject(s) - v3 loop , binding site , antibody , neutralizing antibody , molecular dynamics , chemistry , human immunodeficiency virus (hiv) , microbiology and biotechnology , biology , virology , epitope , biochemistry , genetics , computational chemistry
The coreceptor binding site of gp120 plays an important role in HIV entry into host cell. X5 and 17b are typical coreceptor binding site antibodies with the ability to broadly neutralize HIV . Thus, here, to study the neutralizing mechanism of two antibodies and identify the source of two antibodies with different neutralizing ability, we performed molecular dynamics simulations for the complexes of X5 and 17b with gp120 and CD 4. The simulation results indicate X5 and 17b mainly affects CD 4 and coreceptor binding sites. Specifically, for CD 4 binding site ( CD 4bs), the binding of antibodies has different effects on CD 4bs with and without CD 4. However, for coreceptor binding sites, the binding of the antibodies has consistent influence on the region adjacent to loop V3 despite of the simulated systems with or without CD 4. The binding of the antibodies enhances the interactions of gp120 region adjacent to loop V3 with other region of gp120, which are unfavorable for conformational rearrangements of the region adjacent to loop V3 and further binding the coreceptor. Additionally, the interactions of loop V3 and bridging sheet with X5 lead to the close motion of loop V3 in X5 bound form, which further influences the rearrangements in gp120.