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

Laura Silvestri, Flavio Ballante, Antonello Mai, Garland R. Marshall, Rino Ragno

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)2215-2235
Number of pages21
JournalJournal of Chemical Information and Modeling
Volume52
Issue number8
DOIs
StatePublished - Aug 27 2012

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