Modelling of full-length human α4β2 nicotinic receptor by fragmental approach and analysis of its binding modes
Articolo
Data di Pubblicazione:
2008
Citazione:
Modelling of full-length human α4β2 nicotinic receptor by fragmental approach and analysis of its binding modes / A. Pedretti, C. Marconi, C. Bolchi, L. Fumagalli, R. Ferrara, M. Pallavicini, E. Valoti, G. Vistoli. - In: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. - ISSN 0006-291X. - 369:2(2008), pp. 648-653. [10.1016/j.bbrc.2008.02.080]
Abstract:
The objective of the study was to generate a full-length model for the heteropentameric structure of human a4b2 nicotinic receptor.
The monomers structure was derived using a fragmental approach and the pentamer was assembled by protein–protein docking. The
reliability of the model was assessed docking a representative set of known nicotinic ligands. Docking results unveiled that the ligand
affinity depends on key interactions that the ligand’s charged moiety realizes with conserved apolar residues of a4 monomer, whereas
the H-bond acceptor group interacts with a less conserved and more heterogeneous subpocket, involving polar residues of b2 subunit.
The consistency of docking results and the agreement with the experimental data afford an encouraging validation for the proposed
model and emphasize the soundness of such a fragmental approach to model any transmembrane protein.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Fragmental modelling; Homology modelling; Molecular docking; Nicotine; Nicotinic receptors
Elenco autori:
A. Pedretti, C. Marconi, C. Bolchi, L. Fumagalli, R. Ferrara, M. Pallavicini, E. Valoti, G. Vistoli
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