Structural and energetic profiling of SARS-CoV-2 receptor binding domain antibody recognition and the impact of circulating variants
Fig 2
High resolution mapping and clustering of SARS-CoV-2 RBD antibody binding.
RBD residue contact profiles were generated for each antibody based on number of antibody atomic contacts for each RBD residue within a 5 Å distance cutoff. RBD residues and antibodies are ordered using hierarchical clustering analysis, with dendrograms shown on top and left. The antibodies are separated into four major clusters based on contact profiles, and cluster numbers (1–4) are indicated on left. Contacts in heatmap are colored by number of RBD residue antibody atomic contacts, as indicated in the key. For reference, antibody type (Antibody: heavy-chain antibody, Nanobody: single-chain antibody), binding to RBD-closed spike conformation (Closed spike), ability to block ACE2 binding (ACE2 block), SARS-CoV-2 neutralization or SARS-CoV-2/SARS-CoV-1 cross-neutralization (“Y” and “Cross”, respectively, under Neutralization), and interface buried surface area (BSA, Å2) are shown on the left sidebars. Closed spike binding and ACE2 blocking were calculated based on the structures, as described in the Methods. The top bar above the heatmap indicates RBD residues contacted by ACE2 (5 Å distance cutoff) in an ACE2-RBD complex structure (PDB code 6LZG) [52]. For clarity, 100 RBD residues are shown in heatmap; a heatmap with the full set of 139 contacted RBD residues which was used to cluster the antibodies in this figure is shown in S2 Fig. RBD residues that are mutated in SARS-CoV-2 variants of concern (K417, L452, E484, N501) are labeled at bottom and highlighted with gray boxes in heatmap.