Computer-guided library generation applied to the optimization of single-domain antibodies

Hiroki Akiba, Hiroko Tamura, Jose M.M. Caaveiro, Kouhei Tsumoto

Research output: Contribution to journalArticle

Abstract

Computer-guided library generation is a plausible strategy to optimize antibodies. Herein, we report the improvement of the affinity of a single-domain camelid antibody for its antigen using such approach. We first conducted experimental and computational alanine scanning to describe the precise energetic profile of the antibody-antigen interaction surface. Based on this characterization, we hypothesized that in-silico mutagenesis could be employed to guide the development of a small library for phage display with the goal of improving the affinity of an antibody for its antigen. Optimized antibody mutants were identified after three rounds of selection, in which an alanine residue at the core of the antibody-antigen interface was substituted by residues with large side-chains, generating diverse kinetic responses, and resulting in greater affinity (>10-fold) for the antigen.

Original languageEnglish
Pages (from-to)423-431
Number of pages9
JournalProtein engineering, design & selection : PEDS
Volume32
Issue number9
DOIs
Publication statusPublished - Dec 31 2019

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Biochemistry
  • Molecular Biology

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