侧链合规偏好控制蛋白质之间的相互作用
Andrew M Watkins, Richard Bonneau1, Paramjit S Arora
1Center for Computational Biology, Simons Foundation , New York, New York 10010, United States.
Journal of the American Chemical Society
|August 3, 2016
概括
蛋白质的二次结构不会决定蛋白质复合体的结合能量. 相反,特定的侧链形状或旋转体是结合特异性的关键驱动因素,并为设计新的蛋白质-蛋白质相互作用抑制剂提供了见解.
科学领域:
- 生物化学
- 结构生物学
- 计算生物学
背景情况:
- 蛋白质的次要结构 (例如,α螺旋,β片) 提供了蛋白质界面上的残留物呈现的框架.
- 二次结构的形成由脊柱二面角控制,这表明对复杂结构的残留物选择有潜在的影响.
研究的目的:
- 研究蛋白质二次结构与蛋白质复合物形成中的残留物重要性之间的关系.
- 要确定脊柱形状或侧链形状是否是结合能和特异性的主要决定因素.
主要方法:
- 对已知蛋白质-蛋白质复合物的结合能量的残留物贡献的分析.
- 在关键结合的残留物中检查侧链形状偏好 (旋转基).
- 侧链旋转体与结合能量和特异性的相关性.
主要成果:
- 有限的残留物对结合能量有很大的贡献,不论骨干结构或次要结构类型如何.
- 侧链形状,特别是采用首选的旋转,被发现是结合特异性的重要决定因素.
- 在绑定接口中丰富的特定侧链旋转器.
结论:
- 蛋白质与蛋白质相互作用中的结合能量和特异性主要由侧链构造而不是二次结构骨干构造驱动.
- 首选的旋转基因在确定结合性表位和确保特异性方面发挥着至关重要的作用.
- 这些发现为针对蛋白质与蛋白质相互作用的皮胺抑制剂的合理设计提供了基础.
相关概念视频
Protein Folding
129.8K
Overview
129.8K
Protein Folding
12.1K
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...
12.1K
Protein Folding
36.2K
36.2K
Protein-protein Interfaces
15.0K
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...
15.0K
Protein-Protein Interfaces
4.6K
4.6K
Ligand Binding Sites
15.7K
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...
15.7K


