Dense surface glycosylation on the HIV-1 envelope (Env) protein acts as a shield from the adaptive immune system. However, the molecular complexity and flexibility of glycans make experimental studies a challenge. Here we have integrated high-throughput atomistic modeling of fully glycosylated HIV-1 Env with graph theory to capture immunologically important features of the shield topology. This is the first complete all-atom model of HIV-1 Env SOSIP glycan shield that includes both oligomannose and complex glycans, providing results which are physiologically more relevant than the previous models with uniform glycosylation. This integrated approach including quantitative comparison with cryo-electron microscopy data provides hitherto unexplored details of the native shield architecture and its difference from the high-mannose glycoform. We have also derived a measure to quantify the shielding effect over the antigenic protein surface that defines regions of relative vulnerability and resilience of the shield and can be harnessed for rational immunogen design.

中文翻译：

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在原子细节上对HIV-1天然糖盾的弹性和脆弱性的量化

HIV-1包膜（Env）蛋白上的密集表面糖基化作用可抵御适应性免疫系统。但是，聚糖的分子复杂性和柔韧性使实验研究成为一个挑战。在这里，我们使用图论对完全糖基化的HIV-1 Env的高通量原子建模进行了集成，以捕获屏蔽拓扑的免疫学重要特征。这是HIV-1 Env SOSIP聚糖屏蔽的第一个完整的全原子模型，其中包括低聚甘露糖和复杂的聚糖，提供的结果比以前具有均匀糖基化模型的生理意义更强。这种综合方法包括与冷冻电子显微镜数据的定量比较，提供了天然屏蔽结构及其与高甘露糖糖型的差异的迄今未探索的细节。