Homology Modeling and Receptor-Based 3D-QSAR Study of Carbonic Anhydrase IX

• Published in: Journal of chemical information and modeling Vol. 47; no. 6; pp. 2253 - 2262
• Main Authors: Tuccinardi, Tiziano, Ortore, Gabriella, Rossello, Armando, Supuran, Claudiu T, Martinelli, Adriano
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.11.2007
• Subjects: Amino Acid Sequence; Animals; Cancer; Carbonic Anhydrase Inhibitors - chemistry; Carbonic Anhydrase Inhibitors - metabolism; Carbonic Anhydrase Inhibitors - pharmacology; Carbonic Anhydrases - chemistry; Carbonic Anhydrases - classification; Carbonic Anhydrases - metabolism; Computer Simulation; Conserved Sequence; Crystallography, X-Ray; Gene expression; Humans; Imaging, Three-Dimensional; Isoenzymes - chemistry; Isoenzymes - classification; Isoenzymes - metabolism; Ligands; Mice; Models, Molecular; Molecular Sequence Data; Molecules; Quantitative Structure-Activity Relationship; Sequence Alignment; Structural Homology, Protein; Studies; Surface Properties
• ISSN: 1549-9596; 1549-960X
• DOI: 10.1021/ci700214j

Carbonic anhydrase (CA) IX is a very interesting subject for study due to its overexpression in cancer and its expression in very few normal tissues. There are not yet experimental 3D structures of the catalytic domain of this isozyme, and only a few computational studies have been reported. A homology model of CA IX was developed, and using Gold software 124 CA IX inhibitors were docked. The best poses of the ligands were then used as an alignment tool for the development of the first reported CA IX 3D-QSAR model. The obtained results confirm the reliability of the constructed CA IX model and the proposed computational strategy for investigating CAs.