吸收分布代谢分泌和毒性属性预测利用预训练的自然语言处理模型及其在早期药物开发中的应用
Woojin Jung1, Sungwoo Goo2, Taewook Hwang2,3
1College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea.
Pharmaceuticals (Basel, Switzerland)
|March 28, 2024
概括
应用ChemBERTa,一种自然语言处理 (NLP) 模型,用于药物发现. 与其他架构相比,深度神经网络 (DNN) 模型在新数据上的预测性能优于其他架构,突出了NLP在药品中的潜力.
科学领域:
- 计算化学是一种计算化学.
- 药物发现 药物发现
- 机器学习是机器学习.
背景情况:
- 定量结构-活性关系 (QSAR) 模型在药物发现中对于解释药物结构至关重要.
- 机器学习 (ML) 技术,特别是自然语言处理 (NLP),在这个领域越来越多地被使用.
研究的目的:
- 评估预先训练的NLP模型ChemBERTa在药物发现中的性能.
- 使用物理化学特性和简化分子输入线输入系统 (SMILES) 数据,比较四种不同的模型架构 (DNN,编码器,连接,管道).
主要方法:
- 使用ChemBERTa,一个预训练的NLP模型,用于药物发现任务.
- 开发并比较了四种模型架构:DNN (物理化学特性),编码器 (SMILES + NLP),连接 (SMILES + 特性,并行) 和管道 (SMILES + 特性,顺序).
- 从DrugBank收集了5238条与物理化学和ADMET特征有关的条目.
主要成果:
- 在初始数据集中,编码器模型实现了最高的AUROC (76.0%),超过了DNN (62.4%),连接 (74.9%) 和管道 (68.2%).
- 在外部微小体稳定性数据集上,DNN模型显示出优越的预测能力,AUROC为78%,与编码器 (44%) 和连接 (50%) 相比.
- 这些结果表明,仅依赖结构信息 (SMILES) 的模型可能需要进一步优化.
结论:
- 使用物理化学性质的DNN模型,对新的,未见过的数据进行了更好的概括.
- 该研究强调了NLP在制药应用中的前景,但也指出需要更广泛的数据集来改善模型概括性.
- 对结构数据的替代代代币化策略的进一步研究可能会提高基于NLP的药物发现模型的性能.
相关概念视频
Drug Discovery: Overview
7.9K
Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
7.9K
Preclinical Development: Overview
4.4K
Preclinical development consists of a series of tests that ensure the safety and efficacy of a new therapeutic compound before it is tested in humans. There are four main phases to this process. First, safety pharmacology tests are conducted to ensure the drug does not produce any acutely harmful effects. These tests examine parameters such as bronchoconstriction, cardiac dysrhythmias, blood pressure changes, and ataxia. Next, preliminary toxicological testing is performed to determine the...
4.4K
Structure-Activity Relationships and Drug Design
716
Drug design is a dynamic field that involves discovering and developing new medications based on specific biological targets. This process heavily relies on structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR) to guide the design and optimization of efficient drugs.
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
716
Prodrugs
2.6K
Prodrugs are a class of pharmaceutical compounds that undergo a biotransformation process within the body to be converted into a pharmacologically active drug. Prodrugs are designed to improve the therapeutic properties of the parent drug, such as enhancing bioavailability, increasing stability, or reducing toxicity. The concept of prodrugs revolves around modifying the chemical structure of the original drug to make it more effective or convenient for administration.
Prodrugs help overcome...
Prodrugs help overcome...
2.6K
Factors Influencing Drug Absorption: Disease States and Pharmacology
510
Multiple disease states can significantly influence the oral drug absorption process by affecting blood flow and the functionality of the gastrointestinal (GI) system. Various GI diseases, including conditions that alter GI motility, such as diarrhea, decreased acid secretions (achlorhydria), and infections, have been associated with reduced drug absorption.
Substances such as alcohol and specific drugs, including antineoplastics, can also negatively impact drug absorption. For instance,...
Substances such as alcohol and specific drugs, including antineoplastics, can also negatively impact drug absorption. For instance,...
510
Targets for Drug Action: Overview
6.2K
Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
6.2K


