相关实验视频

Updated: May 30, 2025

Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions

Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions

Published on: December 1, 2020

在药物发现中使用网络合作伙伴进行目标识别时要小心

Dandan Tan¹, Yiheng Chen², Yann Ilboudo³

¹Quantitative Life Sciences Program, McGill University, Montréal, QC, Canada; Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, QC, Canada.

|January 25, 2025

概括

利用人类遗传证据可以改善药物标的识别. 然而,包括蛋白质网络合作伙伴在内,虽然增加了灵敏度,但往往导致精度低,并不能可靠地提高药物标发现.

科学领域:

遗传学遗传学是一个
药理学药理学是指药理学的学科.
生物信息学是一种生物信息学.

背景情况:

识别有效的药物目标至关重要,但具有挑战性,失败率很高.
人类遗传证据显著提高了药物开发的成功率.
以前的研究表明,约50%的FDA批准的药物具有遗传验证的标,如果包括蛋白质网络合作伙伴,则增加到66%.

研究的目的:

为了正式测试使用蛋白质网络合作伙伴用于药物标识的有效性.
评估包括相互作用蛋白质在基因标发现方法的精度和灵敏度的影响.

主要方法:

利用IntAct数据库识别物理相互作用的蛋白质.
应用方法包括外基因组范围的关联研究 (ExWAS),基因组范围的关联研究 (GWAS) 与效应指数和遗传优先分数 (GPS).
评估了识别正控基因的精度,灵敏度和特异性,在有和没有网络合作伙伴的情况下.

主要成果:

包括分子相互作用增加了识别积极控制基因的敏感性.
然而,网络合作伙伴的实际应用受到低精度的限制.
将遗传识别目标扩展到包括网络合作伙伴的范围,并没有改善412个测试特征的药物标识.

结论:

虽然蛋白质网络合作伙伴可以提高目标识别的灵敏度,但它们的低精度限制了实际实用性.
将遗传识别目标扩展到包括网络合作伙伴的范围,由于收益不一致,应谨慎解释.

关键词:

这就是IntAct的意义.字符串dbdb 在线播放发现药物的发现.网络合作伙伴网络合作伙伴蛋白质相互作用蛋白质相互作用

更多相关视频

Author Spotlight: Streamlining Protein Target Prediction and Validation via Molecular Docking and CETSA

Author Spotlight: Streamlining Protein Target Prediction and Validation via Molecular Docking and CETSA

Published on: February 23, 2024

Identification of Small Molecule-binding Proteins in a Native Cellular Environment by Live-cell Photoaffinity Labeling

Identification of Small Molecule-binding Proteins in a Native Cellular Environment by Live-cell Photoaffinity Labeling

Published on: September 20, 2016

相关概念视频

Drug Discovery: Overview

Drug Discovery: Overview

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...

Protein Networks

Protein Networks

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,...

Protein-protein Interfaces

Protein-protein Interfaces

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...

Targets for Drug Action: Overview

Targets for Drug Action: Overview

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...

Drug-Receptor Bonds

Drug-Receptor Bonds

Drug-receptor bonds are formed through various chemical forces when drugs interact with target cells. Covalent bonds, strong and irreversible, are exemplified by DNA-alkylating anticancer agents that inhibit cell division. However, such irreversible drug binding lacks selectivity and can modify the DNA of the surrounding healthy cells. Covalent binding often contributes to tissue toxicity, as seen with chloroform and paracetamol metabolites binding to the liver, causing hepatotoxicity.
In...