通过多态分析和人工智能推进向蛋白质降解
Miquel Duran-Frigola1,2, Marko Cigler1, Georg E Winter1
1CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.
Journal of the American Chemical Society
|January 27, 2023
概括
有针对性的蛋白质降解 (TPD) 提供了一种药物治疗蛋白质组的新方法. 人工智能和多元经济学的进步将有助于克服开发这些新疗法的挑战.
科学领域:
- 生物化学
- 药物发现
- 蛋白质组学
背景情况:
- 人类蛋白质组的药用性有限 (约. 20%) 限制了治疗选择.
- 有针对性的蛋白质降解 (TPD) 成为解决无药性目标的有希望的策略.
- TPD利用小分子诱导目标蛋白与E3连接酶之间的接近,导致蛋白质降解.
研究的目的:
- 审查目前针对蛋白质降解的挑战.
- 探索多态分析和AI/ML在推进TPD中的作用.
- 提出未来TPD发展的路线图.
主要方法:
- 对当前文献和新兴技术的观点和审查.
- 讨论多种经济学数据集成.
- 在药物发现中探索人工智能和机器学习应用.
主要成果:
- 确定了TPD的关键挑战,包括目标的具体性和交付.
- 突出了多组学和AI/ML加速降解器设计和发现的潜力.
- 概述了克服TPD局限性的战略路线图.
结论:
- 这代表了药物发现的重大进步,
- 对于释放TPD的全部潜力至关重要.
- 讨论的路线图适用于小分子降解剂和其他近距离诱导方式.
更多相关视频
05:33High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines
Published on: November 9, 2020
9.9K
10:37Deep Proteome Profiling by Isobaric Labeling, Extensive Liquid Chromatography, Mass Spectrometry, and Software-assisted Quantification
Published on: November 15, 2017
12.0K
相关概念视频
Proteomics
7.6K
A proteome is the entire set of proteins that a cell type produces. We can study proteomes using the knowledge of genomes because genes code for mRNAs, and the mRNAs encode proteins. Although mRNA analysis is a step in the right direction, not all mRNAs are translated into proteins.
Proteomics is the study of proteomes' function. It involves the large-scale systematic study of the proteome to denote the protein complement expressed by a genome. Scientist Mark Wilkins coined the term...
Proteomics is the study of proteomes' function. It involves the large-scale systematic study of the proteome to denote the protein complement expressed by a genome. Scientist Mark Wilkins coined the term...
7.6K
Ribosome Profiling
3.6K
Ribosome profiling or ribo-sequencing is a deep sequencing technique that produces a snapshot of active translation in a cell. It selectively sequences the mRNAs protected by ribosomes to get an insight into a cell’s translation landscape at any given point in time.
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
3.6K
The Proteasome
938
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
938
