深度神经网络用于预测蛋白质-蛋白质相互作用的亲和格局
Reut Meiri1, Shay-Lee Aharoni Lotati2, Yaron Orenstein3,4
1School of Electrical and Computer Engineering, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
iScience
|September 23, 2024
概括
这项研究通过使用深度神经网络来准确预测结合亲和关系,增强了蛋白质-蛋白质相互作用预测. 这种方法扩大了用于治疗开发的深度突变扫描的范围.
科学领域:
- 生物化学 生物化学
- 计算生物学 计算生物学
- 结构生物学 结构生物学
背景情况:
- 蛋白质-蛋白质相互作用 (PPI) 的深度突变扫描 (DMS) 研究往往覆盖有限的突变空间,由于狭窄的亲和度范围.
- 金属蛋白酶-2 (N-TIMP2) 与矩阵金属蛋白酶9 (MMP9CAT) 的组织抑制剂相互作用至关重要,但全面研究具有挑战性.
研究的目的:
- 开发一种方法来定量预测超出传统DMS范围的蛋白质变体的结合亲缘关系.
- 为了克服PPI研究中的狭窄亲和度范围限制,使用N-TIMP2和MMP9CAT作为模型系统.
- 应用深度神经网络 (DNN) 来预测未观察到的野生类型和变体结合亲和关系.
主要方法:
- 设计了N-TIMP2的N-终端氨酸变体,以扩大MMP9CAT的亲和度范围.
- 训练深度神经网络 (DNN) 来根据实验数据预测结合亲和关系.
- 在N-TIMP2变体的独立数据集上验证了预测模型.
主要成果:
- 在预测和观察到的log2丰富率 (ER) 值之间实现了良好的相关性.
- 证明预测的ER值与N-TIMP2变体与MMP9CAT的结合亲和力相关.
- 在一个独立的实验数据集上证实了预测准确性.
结论:
- 开发的DNN方法有效地预测了对未观察到的蛋白质变体的结合亲和关系.
- 这种方法显著推进了蛋白质-蛋白质相互作用预测领域.
- 这些发现对开发针对蛋白质相互作用的新疗法有影响.
更多相关视频
10:21Author Spotlight: Streamlining Protein Target Prediction and Validation via Molecular Docking and CETSA
Published on: February 23, 2024
2.4K
07:08Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
Published on: July 14, 2015
7.3K
相关概念视频
02:04Protein-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
02:26Protein Networks
3.9K
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,...
3.9K
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
02:40Ligand Binding Sites
12.8K
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...
12.8K
02:04Protein-Protein Interfaces
3.7K
3.7K