Computational approaches on angiotensin receptors and their ligands: recent developments and results.
Angiotensin II (AngII) is the major regulator of blood pressure, electrolyte balance, and some endocrine functions related to cardiovascular diseases. Moreover, it has been shown that AngII plays a role in various pathological situations involving tissue remodelling and in cancer. Two distinct subtypes of AngII receptors [type 1 (AT1) and type 2 (AT2)] have been identified, and both belong to the G protein-coupled receptor (GPCR) superfamily. A knowledge of the 3D structure of AT receptors could be of great help in the task of understanding molecular interactions, and in the rational design of specific ligands; however, as GPCRs are membrane-bound proteins, high-resolution structural characterization is still an extremely difficult task. For this reason, great importance has been placed on molecular modelling studies and in particular, on homology modelling (HM) techniques. In this review, we report and analyze the main experimental data and the computational procedures and validation methods used for the construction of the AT receptors, describing in details the most successful results and new trends.
Tuccinardi
Tiziano
T
Dipartimento di Scienze Farmaceutiche, Università di Pisa, via Bonanno 6, 56126 Pisa, Italy.
Martinelli
Adriano
A
D000595:Amino Acid Sequence; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000378:metabolism; D057912:Angiotensin II Type 2 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D019295:Computational Biology / Q000379:methods*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D044140:Receptor, Angiotensin, Type 1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D057912:Angiotensin II Type 2 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D008024:Ligands; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II