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相关概念视频

Behavior of Gas Molecules: Molecular Diffusion, Mean Free Path, and Effusion03:48

Behavior of Gas Molecules: Molecular Diffusion, Mean Free Path, and Effusion

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Although gaseous molecules travel at tremendous speeds (hundreds of meters per second), they collide with other gaseous molecules and travel in many different directions before reaching the desired target. At room temperature, a gaseous molecule will experience billions of collisions per second. The mean free path is the average distance a molecule travels between collisions. The mean free path increases with decreasing pressure; in general, the mean free path for a gaseous molecule will be...
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Diffusion01:12

Diffusion

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Diffusion is the passive movement of substances down their concentration gradients—requiring no expenditure of cellular energy. Substances, such as molecules or ions, diffuse from an area of high concentration to an area of low concentration in the cytosol or across membranes. Eventually, the concentration will even out, with the substance moving randomly but causing no net change in concentration. Such a state is called dynamic equilibrium, which is essential for maintaining overall...
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Facilitated Transport01:19

Facilitated Transport

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The chemical and physical properties of plasma membranes cause them to be selectively permeable. Since plasma membranes have both hydrophobic and hydrophilic regions, substances need to be able to transverse both regions. The hydrophobic area of membranes repels substances such as charged ions. Therefore, such substances need special membrane proteins to cross a membrane successfully. In  facilitated transport, also known as facilitated diffusion, molecules and ions travel across a...
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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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Protein Diffusion in the Membrane01:24

Protein Diffusion in the Membrane

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Proteins show rotational as well as lateral diffusion across the membrane. The lateral diffusion of proteins was confirmed through the cell fusion experiment where mouse and human cells were fused, resulting in hybrid cells. When the human and mouse cells fused, the specific membrane proteins on human and mouse cells were marked with the red and green-fluorescent markers, respectively. Initially, the red and green fluorescence was located on the respective hemisphere of the cell. As time...
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Facilitated Diffusion01:16

Facilitated Diffusion

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The plasma membrane, a critical structure in cellular biology, houses an array of transporters, or carrier proteins, interspersed within its lipid bilayer. These proteins play a crucial role in solute transport through facilitated diffusion, a form of passive diffusion that uses transporters to move the molecules across the membrane.
In this process, substrates such as organic compounds and ions interact with a transporter on one side, triggering conformational changes in proteins that enable...
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SILVR:用于分子生成的引导扩散.

Nicholas T Runcie1, Antonia S J S Mey1

  • 1EaSTCHEM School of Chemistry, University of Edinburgh, Edinburgh EH9 3FJ, U.K.

Journal of chemical information and modeling
|September 19, 2023
PubMed
概括

我们开发了一种新方法,即选择性代潜变量精制 (SILVR),用于生成新药分子. 这种方法条件使用蛋白质碎片生成模型,使得在没有蛋白质结构知识的情况下创建高亲和度化合物.

科学领域:

  • 计算化学是一种计算化学.
  • 药物发现 药物发现
  • 机器学习 机器学习

背景情况:

  • 在药物设计中,产生具有所需特性 (高亲和力,低毒性) 的新型,可合成的药物化合物是一个重大挑战.
  • 现有的机器学习模型用于新的分子生成通常需要广泛的,针对特定目标的调整.

研究的目的:

  • 引入一种新的方法,即选择性代潜变量改进 (SILVR),用于在不需要再培训的情况下调节生成模型.
  • 通过使用基于片段的信息,为特定的蛋白质结合点量身定制的新分子生成.

主要方法:

  • SILVR使用参考数据集中的片段匹配结果对现有的基于扩散的等价变量生成模型进行条件化.
  • 来自COVID Moonshot项目的SARS-CoV-2主要蛋白酶片段数据集被用于条件化.
  • SILVR速率参数控制了条件化的程度,允许生成与输入碎片相似的形状的分子.

主要成果:

  • 适度的SILVR率成功生成了适合蛋白质结合点的新型分子,而无需明确的蛋白质结构输入.
  • 该方法证明了将多达三个碎片合并成新分子的能力,而不会影响底层生成模型的质量.
  • 生成的分子呈现出与原始碎片一致的形状,表明结合部位的成功适应.

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Fabrication of Zero Mode Waveguides for High Concentration Single Molecule Microscopy
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A Simple, Robust, and High Throughput Single Molecule Flow Stretching Assay Implementation for Studying Transport of Molecules Along DNA
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结论:

  • SILVR提供了一种强大的,不需要再培训的方法,用于定向药物设计的条件生成模型.
  • 该方法促进了新型分子的生成,这些新型分子符合蛋白质结合口袋,使用基于片段的调节.
  • SILVR是一种可通用的技术,适用于药物发现中的各种蛋白质标和基于扩散的生成模型.