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

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

研究成果: Contribution to journalArticle査読

抄録

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.

本文言語英語
ページ(範囲)423-431
ページ数9
ジャーナルProtein engineering, design & selection : PEDS
32
9
DOI
出版ステータス出版済み - 12 31 2019

All Science Journal Classification (ASJC) codes

  • バイオテクノロジー
  • バイオエンジニアリング
  • 生化学
  • 分子生物学

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