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相关概念视频

Conserved Binding Sites01:49

Conserved Binding Sites

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Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
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Labeling DNA Probes03:31

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DNA probes are fragments of DNA labeled with a reporter tag to enable their detection or purification. The resulting labeled DNA probes can then hybridize to target nucleic acid sequences through complementary base-pairing, and may be used to recover or identify these regions.
Radioisotopes, fluorophores, or small molecule binding partners like biotin or digoxigenin, are the most widely used reporter tags for labeling DNA probes. These labels can be attached to the probe DNA molecule via...
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Single-Strand DNA Binding Proteins01:03

Single-Strand DNA Binding Proteins

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For successful DNA replication, the unwinding of double-stranded DNA must be accompanied by stabilization and protection of the separated single strands of the DNA. This crucial task is performed by single-strand DNA-binding (SSB) proteins. They bind to the DNA in a sequence-independent manner, which means that the nitrogenous bases of the DNA need not be present in a specific order for binding of SSB proteins to it. The binding of SSB proteins straightens single-stranded DNA (ssDNA) and makes...
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DNA as a Genetic Template02:05

DNA as a Genetic Template

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Two structural features of the DNA molecule provide a basis for the mechanisms of heredity: the four nucleotide bases and its double-stranded nature. The Watson-Crick model of double-helical DNA structure, proposed in 1952, drew heavily upon the X-ray crystallography work of researchers Rosalind Franklin and Maurice Wilkins. Watson, Crick, and Wilkins jointly received the Nobel Prize in Physiology or Medicine for their work in 1962. Franklin was, controversially, excluded from the prize for...
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为DNA编码图书馆构建基于块的绑定预测.

Chris Zhang1, Mary Pitman2, Anjali Dixit2

  • 1Department of Chemistry, University of California, Irvine, 1120 Natural Sciences II, Irvine, California 92697, United States.

Journal of chemical information and modeling
|August 14, 2023
PubMed
概括
此摘要是机器生成的。

本研究引入了信息学工具,通过预测药物发现的有效构建块来改进DNA编码图书馆 (DEL). 开发的模型提高了DEL查数据中的信号噪声比.

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科学领域:

  • 药用化学 医学化学
  • 计算化学的计算化学
  • 药物发现 药物发现 药物发现

背景情况:

  • 用DNA编码的库 (DEL) 能够快速选数百万种化合物.
  • 德尔选具有成本效益,但容易产生噪音,需要计算分析.
  • 改善信号噪声比对于有效的DEL数据解释至关重要.

研究的目的:

  • 开发用于分析DEL查数据的信息工具.
  • 确定设计新的DEL图书馆的生产性构建块.
  • 建立基于构建块行为的化合物结合的预测模型.

主要方法:

  • 利用以前的DEL屏幕的数据来推断建筑块的生产力.
  • 开发了一个基于结合的构建块行为预测化合物结合的原则的模型.
  • 将方法应用于针对可溶性环氧化酶 (sEH) 选的三循环OpenDEL库.

主要成果:

  • 证明类似的构建块表现出形成结合化合物的相似概率.
  • 开发的模型在一个数量级上取得了性能,比在一个持久集上的随机猜测要好一点.
  • 建立了对DEL数据的机器学习模型进行比较的基准.

结论:

  • 信息学工作流可以增强新的DEL库的设计.
  • 该模型为优化DEL活动和提高药物发现效率提供了有价值的工具.
  • 这种方法在利用DEL数据来识别强效药物候选物方面取得了重大进展.