INVESTIGADORES
CAPECE Luciana
artículos
Título:
Coarse-Grained/Molecular Mechanics of the TAS2R38 Bitter Taste Receptor: Experimentally-Validated Detailed Structural Prediction of Agonist Binding
Autor/es:
ALESSANDRO MARCHIORI (PRIMER AUTOR); LUCIANA CAPECE (PRIMER AUTOR); ALEJANDRO GIORGETTI (PRIMER AUTOR); PAOLO GASPARINI ; MAIK BEHRENS; PAOLO CARLONI ; WOLFGANG MEYERHOF
Revista:
PLOS ONE
Editorial:
PUBLIC LIBRARY SCIENCE
Referencias:
Lugar: San Francisco; Año: 2013 vol. 8 p. 64675 - 64675
ISSN:
1932-6203
Resumen:
Bitter molecules in humans are detected by ~25 G protein-coupled
receptors (GPCRs). The lack of atomic resolution structure for any of
them is complicating an in depth understanding of the molecular
mechanisms underlying bitter taste perception. Here, we investigate the
molecular determinants of the interaction of the TAS2R38 bitter taste
receptor with its agonists phenylthiocarbamide (PTC) and
propylthiouracil (PROP). We use the recently developed hybrid Molecular
Mechanics/Coarse Grained (MM/CG) method tailored specifically for GPCRs.
The method, through an extensive exploration of the conformational
space in the binding pocket, allows the identification of several
residues important for agonist binding that would have been very
difficult to capture from the standard bioinformatics/docking approach.
Our calculations suggest that both agonists bind to Asn103, Phe197,
Phe264 and Trp201, whilst they do not interact with the so-called extra
cellular loop 2, involved in cis-retinal binding in the GPCR rhodopsin.
These predictions are consistent with data sets based on more than 20
site-directed mutagenesis and functional calcium imaging experiments of
TAS2R38. The method could be readily used for other GPCRs for which
experimental information is currently lacking.