通过尖端的生成人工智能模型,在类似毒品的化学空间的前沿航行
1'Drug Discovery' Laboratory, Department of Pharmacy, University of Naples Federico II, I-80131 Naples, Italy.
Drug discovery today
|August 5, 2024
概括
深度生成模型 (GMs) 通过创建新型分子来彻底改变药物发现. 这篇评论涵盖了用于化学空间探索的RNN,VAE,GAN,NF和变压器等关键架构.
科学领域:
- 计算化学是一种计算化学.
- 药品化学 药品化学 是一个
- 人工智能在药物发现中的作用
背景情况:
- 深度生成模型 (GMs) 能够产生新型分子,绕过传统的相似性搜索.
- 化学空间 (CS) 的探索对于识别新的候选药物至关重要.
- 现有的方法往往缺乏分子生成过程的透明度.
研究的目的:
- 审查化学空间探索的关键深度生成模型架构.
- 讨论分子表示,培训和评估的关键方面.
- 确定未来的研究方向,以改善药物发现中的生成模型.
主要方法:
- 对五个著名的GM架构进行了审查:循环神经网络 (RNN),变化自编码器 (VAE),生成对抗网络 (GAN),规范化流 (NF) 和变压器.
- 对分子表示策略的分析.
- 检查针对目标的CS探索的培训方法.
- 讨论评估指标,以评估CS覆盖范围.
主要成果:
- 生成模型为导航和扩大化学空间提供了强大的工具.
- 不同的架构 (RNN,VAE,GAN,NF,变压器) 具有独特的优势和挑战.
- 分子表示和训练策略显著影响生成的分子的质量和多样性.
- 目前的模型在解释性和全面的CS覆盖方面面临挑战.
结论:
- 深度生成模型正在改变类似于药物的化学太空探索.
- 需要进一步的研究来提高模型的解释性,完善架构,并开发强大的基准.
- 改进的模型将加速发现具有所需生物特性的分子.
相关概念视频
01:26Drug Discovery: Overview
7.7K
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...
7.7K
01:28Structure-Activity Relationships and Drug Design
687
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...
687
01:16Non-equilibrium in the Cell
4.4K
An important concept in studying metabolism and energy is that of chemical equilibrium. Most chemical reactions are reversible. They can proceed in both directions, releasing energy into their environment in one direction, and absorbing it from the environment in the other direction. The same is true for the chemical reactions involved in cell metabolism, such as the breaking down and building up of proteins into and from individual amino acids, respectively. Reactants within a closed system...
4.4K
01:20Pharmacokinetic Models: Overview
629
Pharmacokinetic models utilize mathematical analysis to achieve a detailed quantitative understanding of a drug's life cycle within the body. They are instrumental in simulating a drug's pharmacokinetic parameters, predicting drug concentrations over time, optimizing dosage regimens, linking concentrations with pharmacologic activity, and estimating potential toxicity.
There are three primary types of models: empirical, compartment, and physiological. Empirical models, with minimal...
There are three primary types of models: empirical, compartment, and physiological. Empirical models, with minimal...
629
01:24Principles of Drug Action
5.9K
Drugs are chemical substances that modify biological responses by interacting with macromolecular targets such as receptors, ion channels, transporters, and enzymes. Pharmacodynamics describes the course of action of drugs leading to the physiological effect at a specific site in the body.
Drugs can be agonists or antagonists. Like the endogenous ligands, agonists always bind and activate the target to produce a cellular response. Agonist binding induces a conformational change which in turn...
Drugs can be agonists or antagonists. Like the endogenous ligands, agonists always bind and activate the target to produce a cellular response. Agonist binding induces a conformational change which in turn...
5.9K
01:21Mechanistic Models: Overview of Compartment Models
76
Mechanistic models, a category encompassing both physiological and compartmental modeling, differ from empirical models' approaches to incorporating known factors about the systems being modeled. Empirical models describe data with minimal assumptions, while mechanistic models aim to provide a robust description of available data by specifying assumptions and integrating known factors about the system. Compartmental analysis is a key example of a mechanistic model in pharmacokinetics and...
76