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相关概念视频

Molecular Models02:00

Molecular Models

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Physical models representing molecular architectures of chemical compounds play essential roles in understanding chemistry. The use of molecular models makes it easier to visualize the structures and shapes of atoms and molecules.
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Drug Discovery: Overview01:26

Drug Discovery: Overview

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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...
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Three-Compartment Open Model01:06

Three-Compartment Open Model

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The three-compartment open model is a pharmacokinetic model used to describe the distribution and elimination of drugs following extravascular administration. It comprises a central compartment representing the plasma and two peripheral compartments. The highly perfused peripheral compartment represents organs and tissues with a rich blood supply, such as the liver, kidneys, and lungs. The scarcely perfused peripheral compartment represents tissues with lower blood supply, such as adipose...
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Passive Diffusion: Overview and Kinetics01:17

Passive Diffusion: Overview and Kinetics

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Passive diffusion is a critical process that allows small lipophilic drugs to cross the cell membrane along a concentration gradient. This mechanism's efficiency depends on four primary factors: the membrane's surface area, the drug's lipid-water partition coefficient, the concentration gradient, and the membrane's thickness.
When administered orally, drugs establish a substantial concentration gradient between the gastrointestinal (GI) lumen and the bloodstream, expediting...
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Physiological Pharmacokinetic Models: Blood Flow-Limited Versus Diffusion-Limited Models00:57

Physiological Pharmacokinetic Models: Blood Flow-Limited Versus Diffusion-Limited Models

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Physiological pharmacokinetic models, often called flow-limited or perfusion models, typically assume a swift drug distribution between tissue and venous blood, creating a rapid drug equilibrium. This premise is based on the idea that drug diffusion is extremely fast, and the cell membrane presents no barrier to drug permeation. In this scenario, where no drug binding occurs, the drug concentration in the tissue equals that of the venous blood leaving the tissue. This greatly simplifies the...
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Theories of Dissolution: The Danckwerts' Model and Interfacial Barrier Model01:09

Theories of Dissolution: The Danckwerts' Model and Interfacial Barrier Model

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Various dissolution theories provide insight into the factors that influence the dissolution rate. Danckwerts' Model suggests that turbulence, rather than a stagnant layer, characterizes the dissolution medium at the solid-liquid interface. In this model, the agitated solvent contains macroscopic packets that move to the interface via eddy currents, facilitating the absorption and delivery of the drug to the bulk solution. The regular replenishment of solvent packets maintains the...
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相关实验视频

Updated: Jun 29, 2025

Author Spotlight: Exploring Cellular Processes by Modeling Ligands in Cryo-EM Maps
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Author Spotlight: Exploring Cellular Processes by Modeling Ligands in Cryo-EM Maps

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双扩散模型可以实现基于目标口袋的3D分子生成和优化.

Lei Huang1,2, Tingyang Xu2, Yang Yu2

  • 1City University of Hong Kong, Hong Kong, SAR, China.

Nature communications
|March 27, 2024
PubMed
概括

我们开发了PMDM,这是一个新的深度生成模型,用于药物发现中高效的3D分子设计. 这种以结构为基础的方法优化了化合物,显示了针对像循环素依赖的激酶2这样的目标的改善活性.

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A Method for Determination and Simulation of Permeability and Diffusion in a 3D Tissue Model in a Membrane Insert System for Multi-well Plates
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相关实验视频

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科学领域:

  • 计算化学是一种计算化学.
  • 药物发现 药物发现
  • 医学中的人工智能.

背景情况:

  • 基于结构的生成化学对于计算机辅助的药物发现至关重要.
  • 传统方法面临着计算效率低下,当前的机器学习模型具有采样瓶.

研究的目的:

  • 开发一种高效的条件深度生成模型,用于针对特定蛋白质标的3D分子生成.
  • 克服现有的in silico药物设计技术的局限性.

主要方法:

  • 开发了PMDM,一种包含本地和全球分子动态的条件等价扩散模型.
  • 利用蛋白质信息有效指导分子生成过程.
  • 使用多个指标对基线模型进行PMDM评估.

主要成果:

  • 与现有模型相比,PMDM在各种评估指标上表现出优越的性能.
  • 应用PMDM优化SARS-CoV-2主要蛋白酶 (Mpro) 和循环素依赖性激酶2 (CDK2) 的化合物.
  • 合成并测试了优化的分子,显示出对CDK2.2的增强体内活性.

结论:

  • 在药物发现中,PMDM为基于结构的3D分子生成提供了一种高效和有效的方法.
  • 该模型对现实世界的应用非常有希望,包括通过改进目标活动来优化化合物.