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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medicinal Chemistry (hsv//eng)

NATURVETENSKAP  -- Kemi (hsv//swe)

NATURAL SCIENCES  -- Chemical Sciences (hsv//eng)

NATURVETENSKAP  -- Data- och informationsvetenskap (hsv//swe)

NATURAL SCIENCES  -- Computer and Information Sciences (hsv//eng)

Nyckelord

Histone Deacetylases

HDAC

3D QSAR

Structure Based Drug Design

COMBINEr

Molecular Docking

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