Histone deacetylase inhibitors: structure-based modeling and isoform-selectivity prediction

J Chem Inf Model. 2012 Aug 27;52(8):2215-35. doi: 10.1021/ci300160y. Epub 2012 Jul 19.


An enhanced version of comparative binding energy (COMBINE) analysis, named COMBINEr, based on both ligand-based and structure-based alignments has been used to build several 3-D QSAR models for the eleven human zinc-based histone deacetylases (HDACs). When faced with an abundance of data from diverse structure-activity sources, choosing the best paradigm for an integrative analysis is difficult. A common example from studies on enzyme-inhibitors is the abundance of crystal structures characterized by diverse ligands complexed with different enzyme isoforms. A novel comprehensive tool for data mining on such inhomogeneous set of structure-activity data was developed based on the original approach of Ortiz, Gago, and Wade, and applied to predict HDAC inhibitors' isoform selectivity. The COMBINEr approach (apart from the AMBER programs) has been developed to use only software freely available to academics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzamides / metabolism
  • Benzamides / pharmacology
  • Drug Design
  • Histone Deacetylase Inhibitors / metabolism*
  • Histone Deacetylase Inhibitors / pharmacology
  • Histone Deacetylases / chemistry*
  • Histone Deacetylases / metabolism*
  • Humans
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / chemistry
  • Isoenzymes / metabolism
  • Models, Molecular*
  • Protein Binding
  • Protein Conformation
  • Pyridines / metabolism
  • Pyridines / pharmacology
  • Quantitative Structure-Activity Relationship
  • Thermodynamics
  • Zinc / metabolism


  • Benzamides
  • Histone Deacetylase Inhibitors
  • Isoenzymes
  • Pyridines
  • entinostat
  • Histone Deacetylases
  • Zinc