Muscarinic receptors: a comparative analysis of structural features and binding modes through homology modelling and molecular docking

Academic Article
Publication Date:
2006
Citation:
Muscarinic receptors: a comparative analysis of structural features and binding modes through homology modelling and molecular docking / A. Pedretti, G. Vistoli, C. Marconi, B. Testa. - In: CHEMISTRY & BIODIVERSITY. - ISSN 1612-1872. - 3:5(2006), pp. 481-501.
abstract:
Three-dimensional models of the five human muscarinic receptors were obtained from their known sequences. Homol. modeling based on the crystallog. structure of bovine rhodopsin yielded models compatible with known results from site-directed mutagenesis studies. The only exceptions were the cytoplasmic loop 3 (CL3) in the five receptors, and the large C-terminal domain in M1. Here, homol. modeling with other closely related proteins allowed to solve these gaps. A detailed comparative discussion of the five models is given. The second part of the work involved docking expts. with the physiol. ligand acetylcholine, again yielding results entirely compatible with results from mutagenesis expts. The study revealed analogies and differences between the five receptors in the residues, and interactions leading to the recognition and binding of acetylcholine
IRIS type:
01 - Articolo su periodico
Keywords:
Muscarinic receptors Role: BSU (Biological study, unclassified), PEP (Physical, engineering or chemical process), PRP (Properties), PYP (Physical process), BIOL (Biological study), PROC (Process) (M1; muscarinic receptor subtype comparative anal. of structural features and binding modes through homol. modeling and mol. docking); Muscarinic receptors Role: BSU (Biological study, unclassified), PEP (Physical, engineering or chemical process), PRP (Properties), PYP (Physical process), BIOL (Biological study), PROC (Process) (M2; muscarinic receptor subtype comparative anal. of structural features and binding modes through homol. modeling and mol. docking); Muscarinic receptors Role: BSU (Biological study, unclassified), PEP (Physical, engineering or chemical process), PRP (Properties), PYP (Physical process), BIOL (Biological study), PROC (Process) (M3; muscarinic receptor subtype comparative anal. of structural features and binding modes through homol. modeling and mol. docking); Muscarinic receptors Role: BSU (Biological study, unclassified), PEP (Physical, engineering or chemical process), PRP (Properties), PYP (Physical process), BIOL (Biological study), PROC (Process) (M4; muscarinic receptor subtype comparative anal. of structural features and binding modes through homol. modeling and mol. docking); Muscarinic receptors Role: BSU (Biological study, unclassified), PEP (Physical, engineering or chemical process), PRP (Properties), PYP (Physical process), BIOL (Biological study), PROC (Process) (M5; muscarinic receptor subtype comparative anal. of structural features and binding modes through homol. modeling and mol. docking); Structure-activity relationship (ligand-binding; muscarinic receptor subtype comparative anal. of structural features and binding modes through homol. modeling and mol. docking); Human; Simulation and Modeling (muscarinic receptor subtype comparative anal. of structural features and binding modes through homol. modeling and mol. docking)
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Authors of the University:
Link to information sheet:
https://air.unimi.it/handle/2434/25911

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Settore CHIM/08 - Chimica Farmaceutica