INSTITUTO DE FISICA DE LIQUIDOS Y SISTEMAS BIOLOGICOS
Unidad Ejecutora - UE
congresos y reuniones científicas
Proteins in aqueous and in physiological solutions. Molecular Dynamics Modeling.
S. N. MONACHESI; M.C. DONNAMARIA; J.R. GRIGERA
Congreso; Reunion Anual de la Sociedad Argentina de Biofísica; 2012
Sociedad Aregntina de Biofísica, Tucuman
Exendin-4, (a 39-residue peptide), first isolated from the saliva of Gila monster displays more than 50 % sequence identity to GLP-1, (30 aminoacids, mammalian hormone), bind in mammalians to the same G-protein coupled receptor and unlike GLP-1 has prolonged duration of action. In the current work by means of molecular dynamics (MD) simulations (GROMACS package) some properties in different solvent media of Glucagon like peptide-1, (GLP-1) and of its longeracting analog exendin-4 (EX4) are studied. These two little proteins, (neuroendocrine hormones) are interesting because of their glucoregulatory action, related with diabetes and obesity control. The MD simulation has proved to be a powerful technique to predict properties of biomolecules in solution. The MD modeling was carried out in nanosecond time scale at normal conditions (T and P) in aqueous and in physiological solutions of EX4 and of GLP-1. In aqueous solutions the SPC/E model is used, while for physiological solutions the counterion dynamics is considered, (monovalent counter ions are placed at substituted water positions). By mean of root mean square RMSD technique the mobility is analyzed as regards the spanned time. The plots show for EX4 the most stable structure. The averaged final conformations show that the peptides form ahelixes in aqueous and physiological media, in agreement with experimental data. The radii of gyration, being a measure of the compactness show the stability of the proteins. The results give some interesting hints for the comparison of methodologies for proteins in aqueous and physiological solutions. MCD and JRG are members of Research Career of Comisión de Investigaciones Científicas, Prov. de Bs As CICPBA-, and of Consejo Nacional de Investigaciones Científicas y Téecnicas CONICET- respectively. SNM is a FCE-UNLP, PHD applicant. Authors gratefully acknowledge support to IFLYSIB (CONICET-UNLP) .MCD also thanks a research personal CIC subsidy.