单克隆抗体与抗原结合的双价分析模型的参数估计和鉴定性分析
Kyle Nguyen1, Kan Li2, Kevin Flores3
1Biomathematics Graduate Program, North Carolina State University, Raleigh, 27607, NC, USA; Center for Research in Scientific Computation, North Carolina State University, Raleigh, 27607, NC, USA.
Analytical biochemistry
|August 7, 2023
概括
我们开发了一种新方法来分析抗原-抗体相互作用,在抗原被固定时使用表面等离子体共振 (SPR). 这种方法提高了用于治疗抗体发现的运动分析的准确性.
科学领域:
- 生物化学 生物化学
- 免疫学 免疫学 免疫学
- 分析化学 分析化学
背景情况:
- 表面等离子体共振 (SPR) 对于表征抗原-抗体相互作用至关重要.
- 标准的SPR分析采用1:1的朗穆尔结合模型,经常使抗体不动.
- 固定抗原需要一种双价分析剂 (1:2) 结合模型,这种模型在现有软件中通常是不可用的或不够的.
研究的目的:
- 开发一种可靠的方法来分析SPR中的1:2结合动力学数据.
- 解决当前SPR软件在双价分析剂结合模型和参数识别方面的局限性.
- 为了促进治疗性抗体发现的准确运动分析.
主要方法:
- 开发了一种使用普通微分方程进行1:2结合动力学分析的新方法.
- 实现了对参数初始化的网格搜索,以克服局部最小值的问题.
- 使用概率分析方法来评估参数的识别性.
主要成果:
- 在使用开发的方法的标准实验设计中确定了一个不可识别的参数.
- 通过模拟指导改进的实验设计,可可靠地估计所有速率常数.
- 新方法成功分析了1:2的结合动力学数据.
结论:
- 开发的方法为使用固定抗原分析SPR数据提供了有价值的工具.
- 解决参数识别和改进实验设计对于准确的动力分析至关重要.
- 这种方法将加速治疗性抗体发现研究.
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