Conformational Heterogeneity of the HIV Envelope Glycan Shield.

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TitleConformational Heterogeneity of the HIV Envelope Glycan Shield.
Publication TypeJournal Article
Year of Publication2017
AuthorsYang, M, Huang, J, Simon, R, Wang, L-X, Mackerell, AD
JournalSci Rep
Date Published2017 Jun 30

To better understand the conformational properties of the glycan shield covering the surface of the HIV gp120/gp41 envelope (Env) trimer, and how the glycan shield impacts the accessibility of the underlying protein surface, we performed enhanced sampling molecular dynamics (MD) simulations of a model glycosylated HIV Env protein and related systems. Our simulation studies revealed a conformationally heterogeneous glycan shield with a network of glycan-glycan interactions more extensive than those observed to date. We found that partial preorganization of the glycans potentially favors binding by established broadly neutralizing antibodies; omission of several specific glycans could increase the accessibility of other glycans or regions of the protein surface to antibody or CD4 receptor binding; the number of glycans that can potentially interact with known antibodies is larger than that observed in experimental studies; and specific glycan conformations can maximize or minimize interactions with individual antibodies. More broadly, the enhanced sampling MD simulations described here provide a valuable tool to guide the engineering of specific Env glycoforms for HIV vaccine design.

Alternate JournalSci Rep
PubMed ID28667249
PubMed Central IDPMC5493700
Grant ListR01 GM070855 / GM / NIGMS NIH HHS / United States