

Title | Conformational Heterogeneity of the HIV Envelope Glycan Shield. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Yang, M, Huang, J, Simon, R, Wang, L-X, Mackerell, AD |
Journal | Sci Rep |
Volume | 7 |
Issue | 1 |
Pagination | 4435 |
Date Published | 2017 Jun 30 |
ISSN | 2045-2322 |
Abstract | 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. |
DOI | 10.1038/s41598-017-04532-9 |
Alternate Journal | Sci Rep |
PubMed ID | 28667249 |
PubMed Central ID | PMC5493700 |
Grant List | R01 GM070855 / GM / NIGMS NIH HHS / United States |