EquiCPI:SE(3) -用于结构意识预测化合物-蛋白质相互作用的等价几何深度学习
Ngoc-Quang Nguyen1,2, Jaewoo Kang1,2
1Department of Computer Science and Engineering, Korea University, Seoul 02841, Republic of Korea.
Journal of chemical information and modeling
|July 2, 2025
概括
EquiCPI使用3D结构准确预测化合物-蛋白相互作用,优于现有方法. 这种几何深度学习框架通过捕获关键的绑定决定因素来增强药物发现.
科学领域:
- 计算机化药物发现.
- 结构生物信息学 结构生物信息学
- 几何深度学习的几何深度学习
背景情况:
- 预测化合物-蛋白相互作用 (CPI) 对药物发现至关重要.
- 当前基于序列的方法往往忽略了关键的3D结构信息,这对于结合亲和关系至关重要.
- 在利用3D结构数据来准确预测CPI方面存在差距.
研究的目的:
- 引入EquiCPI,这是一个新的端到端几何深度学习框架,用于CPI预测.
- 将3D结构信息集成到深度学习模型中,以提高绑定亲和度预测.
- 解决基于序列的方法在计算药物发现中的局限性.
主要方法:
- 使用ESMFold和DiffDock-L生成蛋白质和连接体的3D原子坐标.
- 采用SE(3) -等价神经网络,通过原子点云传递信息.
- 结合物理引导的符合性重新排名和等价特征学习.
- 利用球体波的张量积来对相互作用模式进行层次编码.
主要成果:
- 在BindingDB.上,EquiCPI在亲和力预测方面取得了最先进的表现.
- 该模型展示了在DUD-E数据集上的虚拟选中的竞争性结果.
- EquiCPI有效地捕捉了影响结合亲和力的3D结构决定因素.
结论:
- 通过结合3D结构数据,EquiCPI代表了预测化合物-蛋白相互作用的重大进步.
- 该框架的SE(3)-等价性确保了对分子几何学的稳健处理.
- EquiCPI为加速计算药物发现和开发提供了一个强大的新工具.
相关概念视频
02:04Protein-protein Interfaces
13.5K
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...
13.5K
01:49Conserved Binding Sites
4.4K
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...
4.4K
01:24Protein Organization
7.3K
Proteins are polymers of amino acid residues. They are versatile and responsible for different cellular functions, including DNA replication, molecular transport, catalysis, and structural support. Proteins have a hierarchical structure comprising at least three levels of organization: primary, secondary, and tertiary structure. Some large proteins have a quaternary structure where individual protein subunits are linked together.
The primary structure of a protein is its amino acid sequence....
The primary structure of a protein is its amino acid sequence....
7.3K
01:57Protein Complexes with Interchangeable Parts
2.6K
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...
2.6K
02:27Predicting Molecular Geometry
36.2K
VSEPR Theory for Determination of Electron Pair Geometries
36.2K
02:26Protein Networks
4.1K
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,...
4.1K