Hu Ye, Stumpfe Dagmar, Bajorath Jürgen
Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität , Dahlmannstrasse 2, D-53113 Bonn, Germany.
J Med Chem. 2017 Feb 23;60(4):1238-1246. doi: 10.1021/acs.jmedchem.6b01437. Epub 2016 Dec 21.
Scaffold hopping refers to the computer-aided search for active compounds containing different core structures, which is a topic of high interest in medicinal chemistry. Herein foundations and caveats of scaffold hopping approaches are discussed and recent methodological developments analyzed. Despite the conceptual prevalence of pharmacophore methods for scaffold hopping, a variety of computational approaches have been successfully applied. In recent years, scaffold hopping calculations are increasingly carried out at the level of scaffolds rather than compounds, and scaffold queries increasingly abstract from chemical structures. In addition, relationships between compounds, scaffolds, and biological activities are beginning to be globally explored, beyond individual applications. Going forward, computational scaffold hopping is thought to benefit from the consideration of new scaffold concepts and the development of methods capable of guiding search calculations toward scaffolds that are likely to represent potent compounds.
骨架跃迁是指通过计算机辅助搜索含有不同核心结构的活性化合物，这是药物化学中备受关注的一个话题。本文讨论了骨架跃迁方法的基础和注意事项，并分析了近期的方法学进展。尽管药效团方法在骨架跃迁中概念上较为普遍，但多种计算方法也已成功应用。近年来，骨架跃迁计算越来越多地在骨架层面而非化合物层面进行，骨架查询也越来越脱离化学结构。此外，除了个别应用外，化合物、骨架和生物活性之间的关系也开始得到全面探索。展望未来，计算骨架跃迁有望受益于新骨架概念的考量以及能够将搜索计算导向可能代表强效化合物的骨架的方法的开发。
