在全基因组规模上基于蛋白质-蛋白质相互作用的结构预测
Qiangfeng Cliff Zhang1, Donald Petrey, Lei Deng
1Howard Hughes Medical Institute, Columbia University, New York, New York 10032, USA.
Nature
|October 2, 2012
概括
预测蛋白质与蛋白质相互作用 (PPI) 对于理解细胞调节至关重要. 与其他方法相比,使用3D结构数据显著提高了PPI预测的准确性和覆盖范围.
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.
- 系统生物学 系统生物学
背景情况:
- 鉴定蛋白与蛋白相互作用 (PPI) 是了解细胞机制的关键.
- 目前的方法,如酵母双混合和计算方法,在准确性和完整性方面存在局限性.
- 全基因组PPI谱的开发是一个持续的挑战.
研究的目的:
- 评估用于预测PPI的三维 (3D) 结构信息的有效性.
- 开发和评估一种用于PPI预测的新型算法 (PrePPI).
- 使用结构数据识别新的,具有生物学意义的PPI.
主要方法:
- 利用了3D结构信息,包括同质模型.
- 开发了PrePPI算法,将结构数据与其他功能线索集成在一起.
- 在预测中使用蛋白质之间的几何关系 (近距离和远距离).
主要成果:
- 基于3D结构信息的预测在准确性和覆盖率方面超过了非结构证据.
- PrePPI算法实现的准确性与高通量实验相提并论.
- 产生了超过3万个酵母和30万个人类高可靠性PPI.
- 实验验证证了PrePPI能够预测新奇有趣的PPI的能力.
结论:
- 三维结构信息是蛋白质与蛋白质相互作用的强大预测器.
- 预PPI算法为大规模的PPI识别提供了一个强大而准确的方法.
- 结构性见解,包括同质模型和几何分析,对于推进PPI研究至关重要.
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相关概念视频
Protein and Protein Structure
Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
A protein's shape is critical to its function. For example, an enzyme can...
A protein's shape is critical to its function. For example, an enzyme can...
Protein-protein Interfaces
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 polypeptide...
Conserved 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...
Protein Networks
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,...
Protein-Protein Interfaces
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 polypeptide...
Protein Networks
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,...
