利用深厚的统计潜力来对蛋白质-相互作用进行生物物理评分
De-Jun Jiang1,2,3, Hui-Feng Zhao1, Hong-Yan Du1
1College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
Acta pharmacologica Sinica
|October 1, 2025
概括
DeepPpIScore是一个新的评分功能,通过使用几何深度学习来增强蛋白质-相互作用预测. 它准确地建模了3D分子结构,以更好地了解结合机制和疗法.
科学领域:
- 生物化学和结构生物学
- 计算生物学和生物信息学
- 药物发现和开发 药物发现和开发
背景情况:
- 蛋白质-相互作用 (PPI) 对细胞功能至关重要.
- 目前用于PPI的机器学习方法往往缺乏3D空间理解.
- 现有的蛋白质接得分功能精度有限.
研究的目的:
- 为蛋白质-相互作用 (PPI) 开发一种新的,高精度的评分函数 (SF).
- 改进PPI的3D结构和结合特征的预测.
- 推进对用于治疗的分子相互作用的理解.
主要方法:
- 开发了DeepPpIScore,这是一个利用无监督几何深度学习和物理启发的统计潜力的评分功能.
- 仅在精选的实验性蛋白质-质复合结构上训练模型.
- 评估任务的性能,包括对形状的预测,结合性亲缘关系的预测和结合对的识别.
主要成果:
- 根据DeepPpIScore的研究结果,DeepPpIScore与先进的方法 (包括AlphaFold-Multimer 2.3.3) 相比,表现优越或可比.
- 在预测结模式方面取得了很好的结果,表现优于AlphaFold-Multimer 2.3.3.
- 展示了关于蛋白质接口热点,非共价相互作用和结合能量的解释性.
结论:
- DeepPpIScore为分析蛋白质-相互作用提供了一个强大而易于解释的工具.
- 该方法提升了3D蛋白质-化合物的预测精度.
- 这种方法对开发新型疗法具有重大潜力.
相关概念视频
02:04Protein-protein Interfaces
14.4K
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...
14.4K
02:26Protein Networks
4.5K
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,...
4.5K
01:33Proteomics
9.3K
A proteome is the entire set of proteins that a cell type produces. We can study proteomes using the knowledge of genomes because genes code for mRNAs, and the mRNAs encode proteins. Although mRNA analysis is a step in the right direction, not all mRNAs are translated into proteins.
Proteomics is the study of proteomes' function. It involves the large-scale systematic study of the proteome to denote the protein complement expressed by a genome. Scientist Mark Wilkins coined the term...
Proteomics is the study of proteomes' function. It involves the large-scale systematic study of the proteome to denote the protein complement expressed by a genome. Scientist Mark Wilkins coined the term...
9.3K
01:49Conserved Binding Sites
5.0K
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...
5.0K