竞争性相互作用的蛋白质占据中心服从一个简单的排队法则
Yuming Jiang1, Antun Skanata1,2, Liviu Movileanu1,2,3,4
1Department of Physics, Syracuse University, 201 Physics Building, Syracuse, New York 13244-1130, United States.
The journal of physical chemistry. B
|September 24, 2025
概括
由于多个蛋白质连接体 (PL) 和它们的相互作用,预测蛋白质中心占用是复杂的. 新的队列理论模型量化了枢纽占用率,揭示了连接体度如何影响竞争性蛋白质-蛋白质相互作用 (PPI) 和受体结合.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 系统生物学 系统生物学
背景情况:
- 蛋白质枢纽及其连接体调解关键的细胞信号通路.
- 具有不同亲和度和度的复杂配体混合物挑战了枢纽占用率的预测.
- 了解蛋白质与蛋白质相互作用 (PPI) 对细胞功能和疾病至关重要.
研究的目的:
- 在复杂的配体混合物中开发蛋白质枢纽占用率的预测模型.
- 量化连接物度和动力学对竞争性PPI的影响.
- 提供对受体结合动态的机械学理解.
主要方法:
- 队列理论应用于模型 PPI 和枢纽占用.
- 对三元和复杂连接体混合物的分析策略的开发.
- 大规模联结体竞争分析的粗粒度方法.
主要成果:
- 配方体度显著影响其他配方体和蛋白质受体之间的竞争PPI.
- 模型根据动力速率常数和连接体度准确预测枢纽占用率.
- 一种粗粒度的方法简化了复杂的联结体-受体相互作用的分析.
结论:
- 排队理论为理解竞争性PPI和枢纽占用提供了一个强大的框架.
- 开发的模型提供了对生化交通和信号动态的定量见解.
- 这项工作对蛋白质分析,药物开发和理解细胞过程具有广泛的影响.
相关概念视频
Quantitative Aspects of Drug-Receptor Interaction
1.7K
The receptor occupancy theory connects a drug's response to the number of occupied receptors. With higher drug concentrations, more receptors are occupied, leading to increased responses. The formation of drug-receptor complexes involves association and dissociation rates, which reach equilibrium when the forward and backward reactions are equal. The equilibrium association constant (Ka) and its inverse, the equilibrium dissociation constant (Kd), indicate drug affinity. Higher Ka and lower...
1.7K
Cooperative Allosteric Transitions
8.6K
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
8.6K
Cooperative Allosteric Transitions
2.6K
2.6K
Cooperative Allosteric Transitions
3.0K
3.0K
Protein Complexes with Interchangeable Parts
2.9K
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...
2.9K
Protein Complexes with Interchangeable Parts
2.1K
2.1K


