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Binding Site Druggability Assessment in Fragment-Based Drug Design

  • Yu Zhou
  • Niu HuangEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1289)

Abstract

Target druggability refers to the propensity that a particular target is amenable to bind high-affinity drug-like molecules. A robust yet accurate computational assessment of target druggability would greatly benefit the fields of chemical genomics and drug discovery. Here, we illustrate a structure-based computational protocol to quantitatively assess the target binding-site druggability via in silico screening a fragment-like compound library. In particular, we provide guidelines, suggestions, and critical thoughts on different aspects of this computational protocol, including: construction of fragment library, preparation of target structure, in silico fragment screening, and analysis of druggability.

Key words

Druggability assessment Fragment screening Molecular docking MM-GB/SA rescoring Hit rate 

Notes

Acknowledgement

The Chinese Ministry of Science and Technology “973” Grant 2011CB812402 (to N.H.) is acknowledged for financial support, Shoichet Lab at UCSF for the DOCK3.5.54 program and Jacobson Lab at UCSF for PLOP.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Dr. Niu Huang’s LabNational Institute of Biological Sciences, BeijingBeijingPeople’s Republic of China

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