Issue 41, 2021

Computational maturation of a single-domain antibody against Aβ42 aggregation

Abstract

The expansion of structural databases and the increase in computing power are enabling approaches for antibody discovery based on computational design. It has already been shown that it is possible to use this approach to generate antibodies for specific epitopes on challenging targets. Here we describe an application of this procedure for antibody maturation through the computational design of mutational variants of increased potency. We illustrate this procedure in the case of a single-domain antibody targeting an epitope in the N-terminal region of Aβ42, a peptide whose aggregation is closely associated with Alzheimer's disease. We show that this approach enables the generation of an antibody variant with over 200-fold increased potency against the primary nucleation process in Aβ42 aggregation. Our results thus demonstrate that potentiated antibody variants can be obtained by computational maturation.

Graphical abstract: Computational maturation of a single-domain antibody against Aβ42 aggregation

Supplementary files

Article information

Article type
Edge Article
Submitted
28 Jūl. 2021
Accepted
23 Aug. 2021
First published
07 Okt. 2021
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2021,12, 13940-13948

Computational maturation of a single-domain antibody against Aβ42 aggregation

J. Lin, C. Figazzolo, M. A. Metrick, P. Sormanni and M. Vendruscolo, Chem. Sci., 2021, 12, 13940 DOI: 10.1039/D1SC03898B

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