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 physiologically relevant insights of the glycan shield. 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.

HIV-1 包膜 (Env) 蛋白上的密集表面糖基化充当了适应性免疫系统的屏障。然而，聚糖的分子复杂性和灵活性给实验研究带来了挑战。在这里，我们将完全糖基化的 HIV-1 Env 的高通量原子建模与图论相结合，以捕获屏蔽拓扑的免疫学重要特征。这是第一个完整的 HIV-1 Env SOSIP 聚糖屏蔽的全原子模型，其中包括低聚甘露糖和复杂聚糖，提供了聚糖屏蔽的生理相关见解。这种集成方法包括与冷冻电子显微镜数据的定量比较，提供了迄今为止未探索的天然屏蔽结构的细节及其与高甘露糖糖型的差异。我们还得出了一种量化抗原蛋白表面屏蔽效应的方法，该方法定义了屏蔽的相对脆弱性和弹性区域，并可用于合理的免疫原设计。