Structural trends in antibody-antigen binding interfaces: a computational analysis of 1833 experimentally determined 3D structures.

Autor:	Madsen AV; Department of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, Denmark., Mejias-Gomez O; Department of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, Denmark., Pedersen LE; Department of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, Denmark., Preben Morth J; Department of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, Denmark., Kristensen P; Department of Chemistry and Bioscience, Aalborg University, Aalborg, Denmark., Jenkins TP; Department of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, Denmark., Goletz S; Department of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, Denmark.
Jazyk:	angličtina
Zdroj:	Computational and structural biotechnology journal [Comput Struct Biotechnol J] 2023 Dec 05; Vol. 23, pp. 199-211. Date of Electronic Publication: 2023 Dec 05 (Print Publication: 2024).
DOI:	10.1016/j.csbj.2023.11.056
Abstrakt:	Antibodies are attractive therapeutic candidates due to their ability to bind cognate antigens with high affinity and specificity. Still, the underlying molecular rules governing the antibody-antigen interface remain poorly understood, making in silico antibody design inherently difficult and keeping the discovery and design of novel antibodies a costly and laborious process. This study investigates the characteristics of antibody-antigen binding interfaces through a computational analysis of more than 850,000 atom-atom contacts from the largest reported set of antibody-antigen complexes with 1833 nonredundant, experimentally determined structures. The analysis compares binding characteristics of conventional antibodies and single-domain antibodies (sdAbs) targeting both protein- and peptide antigens. We find clear patterns in the number antibody-antigen contacts and amino acid frequencies in the paratope. The direct comparison of sdAbs and conventional antibodies helps elucidate the mechanisms employed by sdAbs to compensate for their smaller size and the fact that they harbor only half the number of complementarity-determining regions compared to conventional antibodies. Furthermore, we pinpoint antibody interface hotspot residues that are often found at the binding interface and the amino acid frequencies at these positions. These findings have direct potential applications in antibody engineering and the design of improved antibody libraries. Competing Interests: The authors declare that they have no conflict of interest. (© 2023 The Authors.)
Databáze:	MEDLINE
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