MOAST:行动机制相似性工具
Akshar Lohith1,2,3, Derfel Terciano1,3, Adam Murray1,2
1Department of Chemistry and Biochemistry, University of California, Santa Cruz, 1156 High Street, Santa Cruz, 95064, CA, USA.
bioRxiv : the preprint server for biology
|September 26, 2025
概括
MOAST (作用机制相似性工具) 为药物发现提供了快速的作用机制假设. 这个计算工具通过提供统计严格和可解释的MOA预测来帮助资源有限的研究人员.
科学领域:
- 计算化学是一种计算化学.
- 药物发现 药物发现
- 生物信息学是一种生物信息学.
背景情况:
- 确定天然产品的作用机制 (MOA) 是药物发现的一个关键挑战.
- 传统的方法往往资源密集,或需要大量的计算能力和数据.
- 对于那些拥有较小的复合库或有限的计算访问的研究人员来说,现有的方法面临着局限性.
研究的目的:
- 介绍MOAST (行动机制相似性工具),这是一个新的计算工作流程,用于快速生成MOA假设.
- 解决传统和复杂的机器学习方法的限制,以确定MOA.
- 为MOA预测提供一个可访问和统计严格的解决方案.
主要方法:
- 开发了一个以BLAST为灵感的计算工作流程,MOAST.
- 实施了两个互补的方法:用于统计显著性的内核密度估计 (KDE) 和用于多类预测的CatBoost分类器.
- 利用来自HeLa和A549细胞系的细胞学分析数据进行模型培训和验证.
主要成果:
- 在约300个MOA类中,MOAST在前5个预测中实现了22%的准确性.
- CatBoost分类器显示出10%的平衡准确度,显著超过之前文献基准 (~3%).
- 确定了可靠结果的0.8的预测概率值,在特征减少技术中表现强.
结论:
- MOAST为MOA确定提供了一种实用且易于使用的解决方案,将表型查和计算方法相结合.
- 该工具使资源有限的研究人员能够高效可靠地生成MOA假设.
- MOAST保持了统计的严谨性和可解释性,促进了药物发现工作.
更多相关视频
13:18Network Pharmacology Prediction and Experimental Validation of Trichosanthes-Fritillaria thunbergii Action Mechanism Against Lung Adenocarcinoma
Published on: March 3, 2023
1.7K
07:25In Vitro Methods for Comparing Target Binding and CDC Induction Between Therapeutic Antibodies: Applications in Biosimilarity Analysis
Published on: May 4, 2017
18.2K
相关概念视频
01:28Structure-Activity Relationships and Drug Design
1.6K
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...
1.6K
01:18Indirect-Acting Cholinergic Agonists: Mechanism of Action
2.5K
Indirect-acting cholinergic agonists work by interacting with an enzyme called acetylcholinesterase (AChE) in the synaptic cleft. They can be reversible or irreversible inhibitors and have different effects on the enzyme.
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex,...
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex,...
2.5K
03:06Reaction Mechanisms
30.4K
Chemical reactions often occur in a stepwise fashion, involving two or more distinct reactions taking place in a sequence. A balanced equation indicates the reacting species and the product species, but it reveals no details about how the reaction occurs at the molecular level. The reaction mechanism (or reaction path) provides details regarding the precise, step-by-step process by which a reaction occurs.
For instance, the decomposition of ozone appears to follow a mechanism with two steps:
For instance, the decomposition of ozone appears to follow a mechanism with two steps:
30.4K
01:26Targets for Drug Action: Overview
9.9K
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...
9.9K
01:24Principles of Drug Action
7.8K
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...
7.8K
01:27Transducer Mechanism: Enzyme-Linked Receptors
3.8K
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
3.8K