Conformational Heterogeneity of the HIV Envelope Glycan Shield

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...

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Autores principales:	Mingjun Yang, Jing Huang, Raphael Simon, Lai-Xi Wang, Alexander D. MacKerell
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cc07305358eb4e378983a70d20f1e10e
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spelling	oai:doaj.org-article:cc07305358eb4e378983a70d20f1e10e2021-12-02T15:05:36ZConformational Heterogeneity of the HIV Envelope Glycan Shield10.1038/s41598-017-04532-92045-2322https://doaj.org/article/cc07305358eb4e378983a70d20f1e10e2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04532-9https://doaj.org/toc/2045-2322Abstract 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.Mingjun YangJing HuangRaphael SimonLai-Xi WangAlexander D. MacKerellNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mingjun Yang Jing Huang Raphael Simon Lai-Xi Wang Alexander D. MacKerell Conformational Heterogeneity of the HIV Envelope Glycan Shield
description	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.
format	article
author	Mingjun Yang Jing Huang Raphael Simon Lai-Xi Wang Alexander D. MacKerell
author_facet	Mingjun Yang Jing Huang Raphael Simon Lai-Xi Wang Alexander D. MacKerell
author_sort	Mingjun Yang
title	Conformational Heterogeneity of the HIV Envelope Glycan Shield
title_short	Conformational Heterogeneity of the HIV Envelope Glycan Shield
title_full	Conformational Heterogeneity of the HIV Envelope Glycan Shield
title_fullStr	Conformational Heterogeneity of the HIV Envelope Glycan Shield
title_full_unstemmed	Conformational Heterogeneity of the HIV Envelope Glycan Shield
title_sort	conformational heterogeneity of the hiv envelope glycan shield
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/cc07305358eb4e378983a70d20f1e10e
work_keys_str_mv	AT mingjunyang conformationalheterogeneityofthehivenvelopeglycanshield AT jinghuang conformationalheterogeneityofthehivenvelopeglycanshield AT raphaelsimon conformationalheterogeneityofthehivenvelopeglycanshield AT laixiwang conformationalheterogeneityofthehivenvelopeglycanshield AT alexanderdmackerell conformationalheterogeneityofthehivenvelopeglycanshield
_version_	1718388794402537472

Conformational Heterogeneity of the HIV Envelope Glycan Shield

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