对抗体-抗原复杂序列-结构预测方法及其系统偏差的比较
Katherine Maia McCoy1, Margaret E Ackerman1,2, Gevorg Grigoryan1,3
1Molecular and Cell Biology Graduate Program, Dartmouth College, Hanover, New Hampshire, USA.
Protein science : a publication of the Protein Society
|August 21, 2024
概括
从序列中预测抗体-抗原复杂结构对于免疫学和治疗学至关重要. AlphaFold-Multimer显示出前景,但需要进一步改进,模型质量与共同的结构图案相联系.
科学领域:
- 结构生物学 结构生物学
- 免疫学 免疫学 免疫学
- 计算生物学 计算生物学
背景情况:
- 对抗体-抗原复杂结构的准确预测对于理解免疫反应和开发抗体疗法至关重要.
- 机器学习 (ML) 的最新进展显著改善了蛋白质-蛋白质相互作用 (PPI) 的预测.
研究的目的:
- 评估和比较六种不同的方法,从氨基酸序列预测抗体-抗原复杂结构.
- 识别当前最有效的计算方法并了解它们的局限性.
主要方法:
- 对六种方法进行了比较分析:AlphaFold-Multimer,RoseTTAFold,ClusPro,SnugDock和AbAdapt. 这六种方法的比较分析.
- 基于从序列数据中对抗体-抗原复合结构的预测准确性的评估.
主要成果:
- 与其他评估方法相比,AlphaFold-Multimer表现出优越的性能.
- 较低质量的AlphaFold-Multimer模型表现出结构偏差,与蛋白质数据库 (PDB) 中的非抗体结构相比,接口上的常见三级基因 (TERM) 较少.
- 更高质量的模型在抗体-抗原接口上显示了更多类似PDB的TERM.
结论:
- 虽然AlphaFold-Multimer是一种领先的方法,但在预测抗体-抗原复杂结构方面仍需要显著改进.
- 目前,PDB中界面几何数据的稀缺性可能会限制基于ML的抗体-抗原相互作用预测方法的有效性.
- 接口TERM的普遍性与预测性能相关,突出了未来方法开发的潜在领域.
相关概念视频
01:25Antibody Structure and Classes
859
Antibodies, also known as immunoglobulins, are produced by B cells in response to foreign substances, such as bacteria and viruses. These proteins are critical for recognizing and neutralizing these substances, protecting the body from potential harm.
The basic structure of an antibody consists of four protein chains: two identical heavy chains and two identical light chains. These chains are held together by disulfide bonds and other non-covalent interactions, forming a Y-shaped structure.
The basic structure of an antibody consists of four protein chains: two identical heavy chains and two identical light chains. These chains are held together by disulfide bonds and other non-covalent interactions, forming a Y-shaped structure.
859
01:10Antibody Structure
59.6K
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...
59.6K
01:49Conserved Binding Sites
4.2K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
4.2K
00:42Cross-reactivity
31.0K
Overview
31.0K