Computational Fragment-Based Drug Design: Current Trends, Strategies, and Applications

Abstract

Fragment-based drug design (FBDD) has become an effective methodology for drug development for decades. Successful applications of this strategy brought both opportunities and challenges to the field of Pharmaceutical Science. Recent progress in the computational fragment-based drug design provide an additional approach for future research in a time- and labor-efficient manner. Combining multiple in silico methodologies, computational FBDD possesses flexibilities on fragment library selection, protein model generation, and fragments/compounds docking mode prediction. These characteristics provide computational FBDD superiority in designing novel and potential compounds for a certain target. The purpose of this review is to discuss the latest advances, ranging from commonly used strategies to novel concepts and technologies in computational fragment-based drug design. Particularly, in this review, specifications and advantages are compared between experimental and computational FBDD, and additionally, limitations and future prospective are discussed and emphasized.

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Acknowledgements

The authors would like to acknowledge the funding supports to the Xie laboratory from the NIH NIDA (P30 DA035778A1) and DOD (W81XWH-16-1-0490). The first author would like to thank Jie in particular, for the consistant support, love, and the memorable and solemn wedding. How lucky the first author is to have Jie as his bride!

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Correspondence to Xiang-Qun (Sean) Xie.

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Guest Editor: Xiang-Qun Xie

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Bian, Y., Xie, XQ.(. Computational Fragment-Based Drug Design: Current Trends, Strategies, and Applications. AAPS J 20, 59 (2018). https://doi.org/10.1208/s12248-018-0216-7

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KEY WORDS

  • fragment-based drug design
  • fragment database
  • drug discovery
  • fragment docking
  • virtual screening