可靠的蛋白质-蛋白质对接与AlphaFold,Rosetta和复制品交换
Ameya Harmalkar1, Sergey Lyskov1, Jeffrey J Gray1,2
1Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD 21218, USA.
bioRxiv : the preprint server for biology
|August 7, 2023
概括
AlphaRED将AlphaFold与基于物理的对接集成,以改善蛋白质复杂结构预测,特别是在具有构造变化的情况下. 这种新方法提高了对具有挑战性的目标的准确性,优于现有的工具.
科学领域:
- 计算生物学是一种计算生物学.
- 结构生物学是结构生物学.
- 生物物理学的生物物理.
背景情况:
- 预测蛋白质复杂结构对于理解生物功能至关重要.
- AlphaFold (AF) 和AF-multimer (AFm) 已经推进了蛋白质结构预测,但在复合体的结构变化方面存在困难.
- 现有的方法取得的成功率有限,特别是在动态蛋白相互作用方面.
研究的目的:
- 为准确的蛋白质复杂结构预测开发一个改进的计算管道.
- 解决深度学习方法在对接期间模拟结构灵活性方面的局限性.
- 为了提高对具有挑战性的蛋白质-蛋白质相互作用的预测准确度.
主要方法:
- 结合AlphaFold用于结构模板生成与基于物理的复制品交换对接算法 (ReplicaDock 2.0).
- 利用AlphaFold预测的局部距离差异测试 (pLDDT) 分数来估计蛋白质的灵活性和对接精度.
- 开发了AlphaRED (AlphaFold启动的复制品交换对接) 管道,以加强对形状变化的采样.
主要成果:
- AlphaRED成功地对接了97个以前失败的AlphaFold预测,这些预测来自对接基准集5.5.5.
- 在63%的基准目标中实现了CAPRI可接受的质量或更好的预测.
- 在难以实现的抗原-抗体点上表现出43%的成功率,明显超过AFm的20%的成功率.
结论:
- 将深度学习 (AlphaFold) 与基于物理学的方法 (ReplicaDock 2.0) 整合在一起,为蛋白质复杂结构预测提供了一个强大的策略.
- AlphaRED有效地模拟了结构变化,提高了对具有挑战性的蛋白质接口的准确性.
- 阿尔法RED管道在计算结构生物学方面取得了重大进展,用于预测动态蛋白相互作用.
相关概念视频
Protein-protein Interfaces
12.5K
Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...
12.5K
Conserved 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
Ligand Binding Sites
12.9K
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
12.9K
Protein Complexes with Interchangeable Parts
2.6K
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
2.6K
Conservation 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
Protein Networks
4.0K
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
4.0K


