抗体碎片的计算突变:从ΔΔG预测中解开侧链
Rika Tandiana1, German P Barletta1,2, Miguel Angel Soler3
1Computational MOdelling of NanosCalE and BioPhysical SysTems─CONCEPT Lab Istituto Italiano di Tecnologia (IIT), Via Melen-83, B Block, 16152 Genoa, Italy.
Journal of chemical theory and computation
|March 6, 2024
概括
准确预测来自突变的抗体结合亲和力变化需要仔细选择侧链重建方法和分子动力学模拟. 这项研究评估了这些计算技术,以改进抗体设计.
科学领域:
- 生物化学和分子生物学
- 计算生物学 计算生物学
- 生物技术是生物技术.
背景情况:
- 抗体和抗体碎片在生物传感和生物治疗中至关重要.
- 结合强度是由接口残留物的组成和排列决定的.
- 计算方法可以预测结构,并评估来自突变的亲和力变化.
研究的目的:
- 独立评估侧链重建和结合亲和度估计方法.
- 在计算型抗体设计中解开结构和亲和力预测的作用.
- 在计算亲和力成熟过程中,改进单个突变的亲和力预测.
主要方法:
- 评估了6种侧链重建方法和10种结合亲和度估计技术.
- 利用了27个具有已知的结构和亲缘关系的抗体/蛋白酶复合物的数据集.
- 在中进行单点突变,最小化和分子动力学模拟,以估计 ΔΔG 值.
主要成果:
- 对突变影响的准确预测在很大程度上依赖于可靠的侧链重建.
- 彻底的分子动力学模拟对于精确的亲和力变化预测至关重要.
- 该研究确定了准确的单点突变发生分析的关键计算步骤.
结论:
- 整合构造性采样和评分有效地表征突变过程.
- 这种方法对于准确的单点突变发生协议至关重要.
- 这些发现对于推进计算抗体设计和工程至关重要.
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...
01:49Conserved Binding Sites
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 analyses the...
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 analyses the...