Molecular Dynamics Simulation of neuroendocrine hormones in different media

S. N. MONACHESI; J.R. GRIGERA; M. C. DONNAMARIA

Villa Carlos Paz

Congreso; SAB 2013 Reunión Anual de la Sociedad Argentina de Biofísica; 2013

Sociedad Argentina de Biofísica

Exendin-4,(EX4),-hormone of 39 aminoacids, first isolated from the Gila monster saliva-displays more than 50 % sequence identity to Glucagon-like peptide-1,(GLP-1)-mammalian hormone of 39 aminoacids-, bind in mammalians to the same G-protein coupled receptor and unlike GLP-1 has prolonged duration of action. In the current work by molecular dynamics (MD) simulations (GROMACS package) some structural and configurational properties of GLP-1 and of its longer?acting analog EX4,in water and physiological solutions are analized. The considered neuroendocrine hormones are interesting because of their glucoregulatory action (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 20 ns at normal conditions in aqueous and in physiological solutions of EX4 and of GLP-1.The SPC/E model for water is used. In physiological solutions, moreover, monovalent counter ions are placed at substituted water positions. The root mean square fluctuation (RMSF) of the Ca atoms give mobility results. The root mean square deviation (RMSD) was already calculated to check the simulations convergence. Also final structures are displayed, showing that EX4 has the most stable structure. The averaged final conformations show the hormones forming ahelixes in the media, in agreement with experimental data. Acknowledgements: SNM is a FCE-UNLP PHD applicant. 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 Técnicas? CONICET-, respectively. Authors gratefully acknowledge support to CONICET&UNLP. MCD also thanks a research personal CICPBA subsidy.