使用DrugLAMP准确且可转移的药物向相互作用预测
Zhengchao Luo1, Wei Wu1, Qichen Sun2
1Department of Big Data and Biomedical AI, College of Future Technology, Peking University, Beijing 100871, China.
Bioinformatics (Oxford, England)
|November 21, 2024
概括
药物LAMP提高药物向相互作用的预测,使用一种新的多模式框架与预训练的语言模型. 这种方法提高了药物发现的准确性和通用性,即使是看不见的药物或目标.
科学领域:
- 计算生物学是一种计算生物学.
- 药物发现 药物发现
- 医学中的人工智能
背景情况:
- 准确的药物标相互作用 (DTI) 预测对于加速药物发现至关重要,特别是对于新型化合物和标.
- 预训练语言模型 (PLM) 和多模式学习为DTI预测提供了有前途的途径,通过利用未标记的数据和整合多种信息来源.
研究的目的:
- 推出DrugLAMP,一个基于PLM的多模式框架,旨在准确和可转移的DTI预测.
- 通过新的融合模块增强模型捕捉复杂相互作用的能力,并改进对现实世界的概括性.
主要方法:
- 药物LAMP集成了分子图和蛋白质序列特征,使用PLM和传统提取器.
- 开发了新的多模式融合模块,包括口袋引导共同注意力 (PGCA) 和配对多模式注意力 (PMMA).
- 采用对比性化合物-蛋白质预训练 (2C2P) 模块来增强跨模式特征对齐和概括.
主要成果:
- 在标准基准和具有挑战性的设置中,DrugLAMP在未见的药物/目标上取得了最先进的表现.
- 该框架表现出强大的解释性和通用性,以注意力地图可视化和成功应用来预测神秘口袋和药物副作用为证据.
- 废弃性研究验证了拟议的PGCA,PMMA和2C2P模块的显著贡献.
结论:
- 药物LAMP代表了DTI预测的重大进步,为药物发现应用提供了更高的准确性和通用性.
- 该框架的多模式方法和新的注意力机制有效地捕捉了复杂的药物-蛋白质关系.
- 代码和数据集的开放可用性促进了该领域的进一步研究和应用.
相关概念视频
Protein-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
Protein-Drug Binding: Determination Methods
132
Determining protein-drug binding can be achieved through indirect and direct methods, each providing valuable insights into the interaction between proteins and drugs.
Indirect methods involve isolating the bound drug from its free form in biological samples such as blood, serum, or plasma. These techniques aim to measure the percentage of drugs bound to proteins. Equilibrium dialysis is a commonly used method where the free drug concentration at equilibrium is measured by separating the bound...
Indirect methods involve isolating the bound drug from its free form in biological samples such as blood, serum, or plasma. These techniques aim to measure the percentage of drugs bound to proteins. Equilibrium dialysis is a commonly used method where the free drug concentration at equilibrium is measured by separating the bound...
132
Quantitative Aspects of Drug-Receptor Interaction
934
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...
934
Ligand Binding Sites
12.7K
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...
12.7K
Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance
30
Drug transporters are critical in drug absorption, distribution, and excretion processes. They should be included in physiological-based pharmacokinetic (PBPK) models, which help predict human drug disposition. However, predicting this is challenging during drug development, especially when liver transport is involved. However, with a realistic representation of body transport processes, an accurate model may be possible.
A recent model describes pravastatin's hepatobiliary excretion,...
A recent model describes pravastatin's hepatobiliary excretion,...
30
Physiological Pharmacokinetic Models: Assumption with Protein Binding
32
Physiological models with protein binding in pharmacokinetics offer a sophisticated approach to understanding drug disposition. These models consider drug-protein interactions, enabling them to effectively predict drug concentrations in different organs and tissues. This precision aids in accurate drug dosing, providing a significant advantage over conventional models. A key process within these models is equilibration, which ensures that drug concentrations achieve a steady state within the...
32


