距离-AF:通过Alphafold2修改预测的蛋白质结构模型,使用用户指定的距离约束
Yuanyuan Zhang1, Zicong Zhang1, Yuki Kagaya2
1Department of Computer Science, Purdue University, West Lafayette, Indiana, 47907, USA.
bioRxiv : the preprint server for biology
|December 18, 2023
概括
距离-AF通过结合氨基酸距离约束来增强蛋白质结构预测. 这种改进的AlphaFold2方法提高了对挑战性蛋白质标的准确性,并有助于将结构融入冷电子显微镜图中.
科学领域:
- 结构生物学是结构生物学.
- 计算生物学是一种计算生物学.
- 生物物理学的生物物理.
背景情况:
- 蛋白质的三维结构对于功能和理解生物过程至关重要.
- 虽然AlphaFold2先进的蛋白质结构预测,但它与复杂的蛋白质折叠和众多形状作斗争.
- 难以实现的目标往往会从当前最先进的模型中产生低于最佳的预测.
研究的目的:
- 为了提高对具有挑战性的目标的蛋白质结构预测准确度.
- 通过整合额外的结构信息来提高AlphaFold2的性能.
- 开发一种帮助解释冷电子显微镜数据的方法.
主要方法:
- 开发了一种改进的AlphaFold2方法,称为距离AF.
- 距离-AF使用来自AlphaFold2的预测结构作为起点.
- 氨基酸之间的距离限制的结合指导了蛋白质折叠的改进.
主要成果:
- 距离-AF在预测蛋白质结构方面表现出更好的准确性.
- 该方法有效地纠正对具有挑战性的蛋白质点的域定向.
- 对于预测的结构,实现了较低的根平均平方偏差 (RMSD).
- 距离AF显示了将蛋白质模型装入冷电子显微镜图中的实用性.
结论:
- 距离AF为现有的蛋白质结构预测工具提供了有价值的增强.
- 距离约束的整合改善了复杂蛋白质折叠的处理.
- 这种方法有望促进结构生物学和冷电子显微镜分析的发展.
相关概念视频
01:25Protein Folding
8.0K
Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
8.0K
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
01:24Protein Organization
6.5K
Proteins are polymers of amino acid residues. They are versatile and responsible for different cellular functions, including DNA replication, molecular transport, catalysis, and structural support. Proteins have a hierarchical structure comprising at least three levels of organization: primary, secondary, and tertiary structure. Some large proteins have a quaternary structure where individual protein subunits are linked together.
The primary structure of a protein is its amino acid sequence....
The primary structure of a protein is its amino acid sequence....
6.5K
02:26Conservation of Protein Domains Over Different Proteins
10.9K
Protein domains are small structurally independent units that are part of a single amino acid chain. Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
10.9K