Everything you need to know about the GLACIER platform — tools, input files, pipeline, and getting started guides.
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Ensemble-based atomistic modeling and quantification of glycan shielding on viral surface proteins.
Many clinically important enveloped viruses mask their surface proteins with a dense layer of host-derived sugars, known as the glycan shield. This sugar coating acts as a powerful immune evasion mechanism by sterically blocking antibody access to the underlying protein surface and, in some cases, directly participating in antibody recognition.
Because these surface glycoproteins are the primary targets of neutralizing antibodies and vaccines, understanding how glycan shielding operates is central to rational immunogen design.
Glycans are notoriously difficult to characterize experimentally. Their intrinsic flexibility, chemical heterogeneity, and rapid motion mean that most structural methods resolve only a small fraction of the glycan mass. What ultimately governs immune accessibility is not a single glycan conformation, but the cumulative, time-averaged effect of many dynamically fluctuating configurations. Computational modeling is therefore essential to bridge this gap.
This platform employs an ensemble-based atomistic modeling approach (building on ALLOSMOD from Sali lab) to capture glycan behavior realistically. Starting from an experimentally determined protein scaffold, individual glycans are modeled at their glycosylation sites and extensively sampled using energy minimization and simulated annealing. Thousands of distinct conformations are generated to form an ensemble that represents the accessible conformational space of the fully glycosylated protein.
Shielding is quantified using the Glycan Encounter Factor (GEF), which measures the probability that an approaching probe—representing the first line of antibody contact—encounters glycan atoms before reaching the protein surface. GEF produces spatial maps that distinguish persistently shielded regions from potential sites of vulnerability.
The glycan shield is analyzed as a network, where glycans are nodes connected by ensemble-averaged volume overlap. Network analysis reveals highly connected glycan clusters, sparsely protected regions, and collective behaviors that shape global immune accessibility.