分析抗原突变如何破坏抗体结合相互作用,以实现快速可靠的抗体再利用。

IF 5.6 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
mAbs Pub Date : 2025-12-01 Epub Date: 2024-12-17 DOI:10.1080/19420862.2024.2440586
Sumaiya Islam, Varun M Chauhan, Robert J Pantazes
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引用次数: 0

摘要

本文章由计算机程序翻译,如有差异,请以英文原文为准。
Analysis of how antigen mutations disrupt antibody binding interactions toward enabling rapid and reliable antibody repurposing.

Antibody repurposing is the process of changing a known antibody so that it binds to a mutated antigen. One of the findings to emerge from the Coronavirus Disease 2019 (COVID-19) pandemic was that it was possible to repurpose neutralizing antibodies for Severe Acute Respiratory Syndrome, a related disease, to work for COVID-19. Thus, antibody repurposing is a possible pathway to prepare for and respond to future pandemics, as well as personalizing cancer therapies. For antibodies to be successfully repurposed, it is necessary to know both how antigen mutations disrupt their binding and how they should be mutated to recover binding, with this work describing an analysis to address the first of these topics. Every possible antigen point mutation in the interface of 246 antibody-protein complexes were analyzed using the Rosetta molecular mechanics force field. The results highlight a number of features of how antigen mutations affect antibody binding, including the effects of mutating critical hotspot residues versus other positions, how many mutations are necessary to be likely to disrupt binding, the prevalence of indirect effects of mutations on binding, and the relative importance of changing attractive versus repulsive energies. These data are expected to be useful in guiding future antibody repurposing experiments.

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来源期刊
mAbs
mAbs 工程技术-仪器仪表
CiteScore
10.70
自引率
11.30%
发文量
77
审稿时长
6-12 weeks
期刊介绍: mAbs is a multi-disciplinary journal dedicated to the art and science of antibody research and development. The journal has a strong scientific and medical focus, but also strives to serve a broader readership. The articles are thus of interest to scientists, clinical researchers, and physicians, as well as the wider mAb community, including our readers involved in technology transfer, legal issues, investment, strategic planning and the regulation of therapeutics.
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