University of Massachusetts Medical School Faculty Publications

Title

An expanded benchmark for antibody-antigen docking and affinity prediction reveals insights into antibody recognition determinants

UMMS Affiliation

Program in Bioinformatics and Integrative Biology

Publication Date

2021-01-29

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Bioinformatics | Computational Biology | Structural Biology

Abstract

Accurate predictive modeling of antibody-antigen complex structures and structure-based antibody design remain major challenges in computational biology, with implications for biotherapeutics, immunity, and vaccines. Through a systematic search for high-resolution structures of antibody-antigen complexes and unbound antibody and antigen structures, in conjunction with identification of experimentally determined binding affinities, we have assembled a non-redundant set of test cases for antibody-antigen docking and affinity prediction. This benchmark more than doubles the number of antibody-antigen complexes and corresponding affinities available in our previous benchmarks, providing an unprecedented view of the determinants of antibody recognition and insights into molecular flexibility. Initial assessments of docking and affinity prediction tools highlight the challenges posed by this diverse set of cases, which includes camelid nanobodies, therapeutic monoclonal antibodies, and broadly neutralizing antibodies targeting viral glycoproteins. This dataset will enable development of advanced predictive modeling and design methods for this therapeutically relevant class of protein-protein interactions.

Keywords

affinity prediction, antibody design, biotherapeutics, monoclonal antibodies, nanobody, protein-protein docking, viruses

DOI of Published Version

10.1016/j.str.2021.01.005

Source

Guest JD, Vreven T, Zhou J, Moal I, Jeliazkov JR, Gray JJ, Weng Z, Pierce BG. An expanded benchmark for antibody-antigen docking and affinity prediction reveals insights into antibody recognition determinants. Structure. 2021 Jan 29:S0969-2126(21)00005-8. doi: 10.1016/j.str.2021.01.005. Epub ahead of print. PMID: 33539768. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Structure (London, England : 1993)

PubMed ID

33539768

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