具有高亲和力的稳定单域抗体的in silico设计
Zhongyao Zhang1, Rob van der Kant2, Iva Marković3
1Switch Laboratory, VIB Center for Brain and Disease Research, VIB, 3000 Leuven, Belgium; Switch Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium; Switch Laboratory, VIB Center for AI & Computational Biology, VIB, 3000 Leuven, Belgium; Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, 3000 Leuven, Belgium.
Structure (London, England : 1993)
|January 10, 2026
概括
新型抗体设计管道EvolveX增强了抗体的稳定性和亲和力. 这种基于结构的方法显著改善了抗体与标蛋白质的结合,为治疗开发提供了强大的工具.
科学领域:
- 生物技术是生物技术.
- 免疫学 免疫学 免疫学
- 结构生物学 结构生物学
背景情况:
- 抗体设计复杂且资源密集.
- 深度学习和生成方法显示出希望,但在实现高亲和度和稳定性方面面临挑战.
- 开发有效的抗体疗法需要克服这些设计局限性.
研究的目的:
- 介绍EvolveX,一个基于结构的抗体设计管道.
- 展示EvolveX提高抗体稳定性和亲和力的能力.
- 重新设计一个VHH抗体,使其与人类Vsig4.4有很高的亲和力.
主要方法:
- 利用了EvolveX,一个利用FoldX实证力场的管道.
- 单域抗体 (VHHs) 的设计的互补性确定区域 (CDRs).
- 应用EvolveX重新设计一个针对VHH的鼠标Vsig4 (mVsig4).
主要成果:
- EvolveX成功地提高了VHHs对mVsig4.4的稳定性和亲和力.
- 在与人类Vsig4.4的结合亲和性方面取得了超过1000倍的改善.
- 射线晶体学证实了设计准确性;NGS分析验证了管道效率.
结论:
- EvolveX克服了当前抗体设计的局限性.
- 为开发具有增强特异性,稳定性和有效性的治疗方法提供了强大的工具.
- 突出了使用实证力场的基于结构的设计的潜力.
相关概念视频
01:10Antibody Structure
65.2K
Overview
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
65.2K
01:31Hybridoma Technology
17.2K
Hybridoma technology is used for the large-scale production of monoclonal antibodies. Monoclonal antibodies bind to only a single antigenic determinant or epitope. Such antibodies are used in research, diagnostics, and disease therapy. The hybridoma technology established in 1975 by Georges Köhler and Cesar Milstein was awarded the Nobel Prize in Medicine in 1984 for revolutionizing research and therapy.
Hybridoma Selection
Commonly used fusion techniques — electroporation,...
Hybridoma Selection
Commonly used fusion techniques — electroporation,...
17.2K