Homology modeling and receptor-based 3D-QSAR study of carbonic anhydrase IX.
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.
Tuccinardi
Tiziano
T
Dipartimento di Scienze Farmaceutiche, Università di Pisa, via Bonanno 6, 56126 Pisa, Italy. tuccinardi@farm.unipi.it
Ortore
Gabriella
G
Rossello
Armando
A
Supuran
Claudiu T
CT
Martinelli
Adriano
A
D000595:Amino Acid Sequence; D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D002256:Carbonic Anhydrases / Q000737:chemistry* / Q000145:classification / Q000378:metabolism*; D003198:Computer Simulation; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D006801:Humans; D021621:Imaging, Three-Dimensional; D007527:Isoenzymes / Q000737:chemistry / Q000145:classification / Q000378:metabolism; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D021281:Quantitative Structure-Activity Relationship; D016415:Sequence Alignment; D040681:Structural Homology, Protein; D013499:Surface Properties
D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D008024:Ligands; D002256:Carbonic Anhydrases