{"title":"The Applications of Computational Tools in PROTAC Development.","authors":"Wangqiu He, Kejia Yan, Zhou Chen, Lianhua Piao, Shan Chang, Ren Kong","doi":"10.2174/0115680266365625250313061523","DOIUrl":null,"url":null,"abstract":"<p><p>The increasing importance of PROTACs (proteolysis-targeting chimeras) has attracted significant attention from both the academic community and industry. PROTACs are heterobifunctional small molecules that can bind to both the protein of interest (POI) and the E3 ubiquitin ligase (E3), inducing ubiquitinated degradation of POI. The unique mechanisms of PROTACs, such as event-driven pharmacology and modulation of protein degradation, provide novel therapeutic modalities for various diseases, including oncology, antiviral therapies, neurodegenerative diseases, acne, and others. Numerous computational methods, including structural prediction, molecular generation, and molecular dynamics simulation, have been applied in the development of PROTAC molecules. This review introduces the fundamental principles of computational tools used in PROTAC design, as well as typical examples validated by experiments.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current topics in medicinal chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0115680266365625250313061523","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
The increasing importance of PROTACs (proteolysis-targeting chimeras) has attracted significant attention from both the academic community and industry. PROTACs are heterobifunctional small molecules that can bind to both the protein of interest (POI) and the E3 ubiquitin ligase (E3), inducing ubiquitinated degradation of POI. The unique mechanisms of PROTACs, such as event-driven pharmacology and modulation of protein degradation, provide novel therapeutic modalities for various diseases, including oncology, antiviral therapies, neurodegenerative diseases, acne, and others. Numerous computational methods, including structural prediction, molecular generation, and molecular dynamics simulation, have been applied in the development of PROTAC molecules. This review introduces the fundamental principles of computational tools used in PROTAC design, as well as typical examples validated by experiments.
期刊介绍：
Current Topics in Medicinal Chemistry is a forum for the review of areas of keen and topical interest to medicinal chemists and others in the allied disciplines. Each issue is solely devoted to a specific topic, containing six to nine reviews, which provide the reader a comprehensive survey of that area. A Guest Editor who is an expert in the topic under review, will assemble each issue. The scope of Current Topics in Medicinal Chemistry will cover all areas of medicinal chemistry, including current developments in rational drug design, synthetic chemistry, bioorganic chemistry, high-throughput screening, combinatorial chemistry, compound diversity measurements, drug absorption, drug distribution, metabolism, new and emerging drug targets, natural products, pharmacogenomics, and structure-activity relationships. Medicinal chemistry is a rapidly maturing discipline. The study of how structure and function are related is absolutely essential to understanding the molecular basis of life. Current Topics in Medicinal Chemistry aims to contribute to the growth of scientific knowledge and insight, and facilitate the discovery and development of new therapeutic agents to treat debilitating human disorders. The journal is essential for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important advances.
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