Open AccessStructural and energetic profiling of SARS-CoV-2 receptor binding domain antibody recognition and the impact of circulating variants
Author(s) -
Rui Yin,
Johnathan D. Guest,
Ghazaleh Taherzadeh,
Ragul Gowthaman,
Ipsa Mittra,
Jane Quackenbush,
Brian G. Pierce
Publication year - 2021
Publication title -
plos computational biology/plos computational biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.628
H-Index - 182
eISSN - 1553-7358
pISSN - 1553-734X
DOI - 10.1371/journal.pcbi.1009380
Subject(s) - antibody , monoclonal antibody , computational biology , epitope , biology , epitope mapping , virology , covid-19 , receptor , genetics , medicine , infectious disease (medical specialty) , disease , pathology
The SARS-CoV-2 pandemic highlights the need for a detailed molecular understanding of protective antibody responses. This is underscored by the emergence and spread of SARS-CoV-2 variants, including Alpha (B.1.1.7) and Delta (B.1.617.2), some of which appear to be less effectively targeted by current monoclonal antibodies and vaccines. Here we report a high resolution and comprehensive map of antibody recognition of the SARS-CoV-2 spike receptor binding domain (RBD), which is the target of most neutralizing antibodies, using computational structural analysis. With a dataset of nonredundant experimentally determined antibody-RBD structures, we classified antibodies by RBD residue binding determinants using unsupervised clustering. We also identified the energetic and conservation features of epitope residues and assessed the capacity of viral variant mutations to disrupt antibody recognition, revealing sets of antibodies predicted to effectively target recently described viral variants. This detailed structure-based reference of antibody RBD recognition signatures can inform therapeutic and vaccine design strategies.