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Conformational Heterogeneity of the HIV Envelope Glycan Shield.

Conformational Heterogeneity of the HIV Envelope Glycan Shield.
Author Information (click to view)

Yang M, Huang J, Simon R, Wang LX, MacKerell AD,


Yang M, Huang J, Simon R, Wang LX, MacKerell AD, (click to view)

Yang M, Huang J, Simon R, Wang LX, MacKerell AD,

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Scientific reports 2017 06 307(1) 4435 doi 10.1038/s41598-017-04532-9

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.

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