IFLYSIB   05383
INSTITUTO DE FISICA DE LIQUIDOS Y SISTEMAS BIOLOGICOS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Molecular dynamics modeling of neuroendocrine hormones in an aqueous an physiological solutions
Autor/es:
M.C. DONNAMARIA; S.N. MONACHESI; J.R. DE XAMMAR ORO; J.R. GRIGERA
Lugar:
Salta
Reunión:
Congreso; SAB 2010, Wokshop CeBEM, 3 rd. Latin American Protein Society Meeting; 2010
Institución organizadora:
SOCIEDAD BIOFISICA ARGENTINA, THE LATIN AMERICAN PROTEIN SOCIETY
Resumen:
 Glucagon like peptide-1, GLP-1, a potent insulin secretagogue, and its longer–acting analog exendin-4 are currently under review as treatment for type 2 diabetes mellitus. Exendin-4, a 39-residue peptide, first isolated from the saliva of Gila monster-an invertebrate species-, and GLP-1, (30–aminoacids, mammalian hormone) possess remarkably sequence homology, and bind to the same G-protein coupled receptor, in mammalians. This study deals with conformational and dynamical properties of these biopeptides, in aqueous and physiological solutions. As a modeling tool, Molecular Dynamics simulation (GROMACS package), is performed in nanosecond time scale at normal conditions (P= 1bar, T= 300K). In aqueous solution the SPC/E model is used. For physiological solutions the counterion dynamics is considered, (monovalent counter ions placed at substituted water positions). The study of flexibility is carried out by root mean square departures of distances of the Ca-atoms compared with the NMR original conformation. The mobility is higher, for the residues located around the ends of the protein chain, and for the GLP-1. The averaged final conformations of the peptides form a-helixes in both media, in agreement with experimental data. The main role of some intra chain hydrogen bonds can be related to the stabilization of the a-helix structures. The results give hints for the comparison of methodologies