通过分子对接和分子动态模拟,对抗IL-8 scFv-10F8-6His与IL-8单体的分子相互作用分析
Fatin Filzah Nur Abdul Kadir1, Muhamad Alif Che Nordin1, Rabiatul Basria S M N Mydin2
1Biological Section, School of Distance Education, Universiti Sains Malaysia, Penang, Malaysia.
Journal of biomolecular structure & dynamics
|October 14, 2023
概括
这项研究确定了抗体中关键的氨基酸残留物,这些抗体结合于对炎症性疾病至关重要的互白素8 (IL-8). 了解这些相互作用有助于开发新的IL-8向疗法.
科学领域:
- 免疫学 免疫学 免疫学
- 结构生物学 结构生物学
- 计算化学计算化学
背景情况:
- 升高的互白素8 (IL-8) 与类风湿性关节炎,牛皮和癌症等炎症状况的不良结果有关.
- 人类单克隆抗体 (HuMab) 10F8和混合体35B11-B是IL-8的向,在湿疹,棕植物性 pustulosis 和大鼠模型中显示出治疗潜力.
- IL-8与抗体之间的分子级结合相互作用,特别是与IL-8的N端的互补性决定区域 (CDR) 循环的作用,需要详细的研究.
研究的目的:
- 为了阐明人类单克隆抗体和介质蛋白8 (IL-8) 之间的分子相互作用.
- 用计算方法识别关键的氨基酸残留物,这些残留物涉及到结合界面.
- 为合理设计针对IL-8的新型,稳定的重组抗体提供见解.
主要方法:
- 采用分子对接来预测初始结合姿势.
- 利用加热和长粗粒度分子动力学 (MD) 模拟 (高达 1000 ns) 来评估结合稳定性和识别关键残留物.
- 进行了残留物分解分析,以量化对结合相互作用的能量贡献.
主要成果:
- 在70 ns加热的MD模拟中,对接复合体显示出稳定的结合.
- 长期MD模拟 (1000 ns) 确定了关键残留物:TYR-53,ASP-99,ARG-100 (重链CDR) 和TYR-33 (轻链CDR) 是高能量贡献者.
- 鉴定出IL-8的LYS11和TYR13对整体结合能很重要.
- 残留物分解分析结果与相互作用分析数据得到证实.
结论:
- 确定了特定的重链和轻链CDR残留物,这些残留物对于抗体与IL-8结合至关重要.
- 突出显示关键的IL-8残留物 (LYS11,TYR13),对结合相互作用至关重要.
- 这些发现为设计改善的抗IL-8抗体用于治疗应用提供了基础.
更多相关视频
08:49Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
Published on: June 20, 2025
237
05:08Application of I TASSER, trRosetta, UCSF Chimera, HADDOCK server, and HEX loria for De Novo and In Silico Design of Proteins
Published on: July 8, 2025
21
相关概念视频
01:10Antibody Structure
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...
01:10Antibody Structure
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...