片段(逻辑)
计算机科学
药物发现
药品
计算生物学
组合化学
数据科学
纳米技术
化学
医学
药理学
生物
生物化学
程序设计语言
材料科学
作者
D. Grenier,Solène Audebert,Jordane Preto,Jean‐François Guichou,Isabelle Krimm
标识
DOI:10.1080/17460441.2023.2234285
摘要
Introduction In fragment-based drug design, fragment linking is a popular strategy where two fragments binding to different sub-pockets of a target are linked together. This attractive method remains challenging especially due to the design of ideal linkers.Areas covered The authors review the types of linkers and chemical reactions commonly used to the synthesis of linkers, including those utilized in protein-templated fragment self-assembly, where fragments are directly linked in the presence of the protein. Finally, they detail computational workflows and software including generative models that have been developed for fragment linking.Expert opinion The authors believe that fragment linking offers key advantages for compound design, particularly for the design of bivalent inhibitors linking two distinct pockets of the same or different subunits. On the other hand, more studies are needed to increase the potential of protein-templated approaches in FBDD. Important computational tools such as structure-based de novo software are emerging to select suitable linkers. Fragment linking will undoubtedly benefit from developments in computational approaches and machine learning models.
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