摘要：SummaryDense 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.Graphical AbstractDisplay OmittedHighlights•HIV-1 Env soluble BG505 SOSIP glycoprotein ensemble modeled with native glycosylation•Cryo-EM comparison suggests core fucose may lead to subtle glycan orientation changes•Native glycan shield topology modeled as a network of glycan-glycan volume overlaps•Glycan Encounter Factor developed to quantify the shielding effect on Env surfaceMolecular Modeling; Virology
