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相关概念视频

Ligand Binding Sites02:40

Ligand Binding Sites

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...
Drug Discovery: Overview01:26

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...
Drug Distribution: Tissue Binding01:21

Drug Distribution: Tissue Binding

Upon entering the systemic circulation, drugs can distribute into the interstitial and intracellular fluid of various tissue cells. This distribution is facilitated by the binding of drugs to different cellular components within tissues, which may lead to drug accumulation in specific areas. Drugs bound to tissue components serve as reservoirs that release free drugs back into the system, prolonging the drug's overall action. However, this accumulation can also result in local toxicity.
For...
Drug Distribution: Plasma Protein Binding01:29

Drug Distribution: Plasma Protein Binding

Drugs predominantly attach to plasma proteins, with only a small percentage remaining unbound. The unbound portion can be calculated as one minus the bound fraction. Acidic drugs form large, inactive complexes by reversibly binding to plasma albumin, which prevents them from diffusing across biological barriers. These drug-protein complexes act as reservoirs for the drugs. As the concentration of unbound drugs decreases, these complexes quickly dissociate to release the free drug, maintaining...
Tissue-Drug Binding: Localization of Drugs and its Significance01:24

Tissue-Drug Binding: Localization of Drugs and its Significance

Body tissues, comprising approximately 40% of the body weight, are crucial in drug distribution and localization. These tissues can serve as drug storage sites, competing with plasma binding sites for drug molecules.
Drugs can bind to different tissue components, enhancing their distribution and localization. The factors influencing drug localization in tissues include the drug's lipophilicity, structural characteristics, tissue perfusion rate, and pH differences. These factors determine the...
Protein-Drug Binding: Determination Methods01:22

Protein-Drug Binding: Determination Methods

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...

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相关实验视频

Updated: Jun 6, 2026

Network Pharmacology Prediction and Metabolomics Validation of the Mechanism of Fructus Phyllanthi against Hyperlipidemia
11:06

Network Pharmacology Prediction and Metabolomics Validation of the Mechanism of Fructus Phyllanthi against Hyperlipidemia

Published on: April 7, 2023

大型图书馆对接用于多药学.

Yujin Wu1, Seth Vigneron1, Joao Braz2

  • 1Department of Pharmaceutical Chemistry, University of California, San Francisco, 1700 fourth St., Byers Hall Suite 508D, San Francisco, California 94158, United States.

Journal of medicinal chemistry
|February 19, 2026
PubMed
概括
此摘要是机器生成的。

大型图书馆对接确定了复杂疾病的双重活性分子. 虽然发现了治疗疼痛,抑郁和焦虑的强效化合物,但优化它们的有效性仍然存在挑战.

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Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
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A Bilingual Computational Workflow for Identifying Potential PLK1 Inhibitors in American Sign Language and English
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Last Updated: Jun 6, 2026

Network Pharmacology Prediction and Metabolomics Validation of the Mechanism of Fructus Phyllanthi against Hyperlipidemia
11:06

Network Pharmacology Prediction and Metabolomics Validation of the Mechanism of Fructus Phyllanthi against Hyperlipidemia

Published on: April 7, 2023

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
08:49

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis

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科学领域:

  • 计算化学是一种计算化学.
  • 药理学 药理学是指药理学的学科.
  • 药物发现 药物发现

背景情况:

  • 多药理学,即同时针对多个生物标,为治疗复杂疾病提供了一个有希望的策略.
  • 识别具有针对特定目标对的联合活性分子对于开发有效的多目标疗法至关重要.

研究的目的:

  • 探索大型图书馆对接的实用性,以发现针对选定目标对的双重活性分子.
  • 通过对alpha2A/SERT,MOR/SERT和alpha2A/MOR目标进行潜在的对接来确定潜在的止痛化合物.

主要方法:

  • 图书馆增长和双重活动分子识别的回顾性分析.
  • 使用对三个目标对进行对接,对9亿个分子库进行潜在的虚拟选.
  • 使用冷电子显微镜 (cryo-EM) 结构确认对接预测的姿势.
  • 在小鼠行为测定中的化合物疗效的体内评估.

主要成果:

  • 对接活动确定了具有低μM到高nM活动的双结合剂,以及对alpha2A/SERT和SERT/MOR目标的高命中率.
  • 来自alpha2A/SERT运动的四胺化合物也表现出对5-HT2A的活性.
  • 化EM证实了对接预测的姿势,但随后的优化在提高功效方面遇到了挑战.
  • α2A/SERT化合物 (z7149) 在无条件位置偏好的情况下在疼痛测试中表现出有效性,并表现出抗抑郁药和焦虑缓解剂类型的行为.

结论:

  • 大型图书馆对接是发现多药物剂的可行策略,为复杂的疾病提供了有希望的结果.
  • 尽管进行了结构验证,但优化已识别的双重活性分子的效能存在重大挑战.
  • 该研究强调了计算对接在推进多药学治疗效益方面的潜力和局限性.