Conformational and dynamical properties of biomolecules in physiological solutions. Molecular dynamics modeling

MC DONNAMARIA; SN MONACHESI; JR.GRIGERA,

Montevideo , Uruguay

Congreso; 6th International Conference on Biological Physics and the 5th Southern Cone Biophysics Congress, anf the 34th Annual Meeting of the Argentinean Biophysical Society,; 2007

Union of Pure and Applied Physics (IUPAP), The International Union for Pure and Applied Biophysics (IUPAB), the Federacion Iberoamericana de Sociedades de Fisica and the Societies of Physics and Biophysics of Argentina, Brazil, UruguayUruguay

CONFORMATIONAL AND DYNAMICAL PROPERTIES OF BIOMOLECULES IN PHYSIOLOGICAL SOLUTIONS. MOLECULAR DYNAMICS MODELING. M.C. Donnamaria ,S.N. Monachesi and J.R.Grigera IFLYSIB,(CIC, CONICET, UNLP), C.C.565, 1900 La Plata, Argentina, donna@iflysib.unlp.edu.arIFLYSIB,(CIC, CONICET, UNLP), C.C.565, 1900 La Plata, Argentina, donna@iflysib.unlp.edu.ar In order to study the hydration and structural properties of Exendin-4 (EX4) and Glucagon like peptide-1, GLP-1, in aqueous and physiological solutions, some molecular dynamics (MD) simulations were carried out using the GROMOS 96 simulation package. Among the biomolecular modeling tools, the MD simulation has proved to be a powerful technique to predict properties of biomolecular systems in solution. The interest in studying these two bioactive peptides is because of the importance of their glucoregulatory action, for which, the both neuroendocrine hormones become potential therapeutic agents in the diabetes and obesity control. Exendin-4, a natural, 39-residue peptide, first isolated from the salivary secretions of Gila Monster-an invertebrate non-mammalian species-, and GLP-1, (30–aminoacids mammalian hormone) possess a remarkable aminoacid sequence homology, and bind to the same G-protein coupled receptor. In mammalians, Ex4 has the advantage that has much longer plasma half-life than GLP-1. This work reports structural and dynamical properties of these two biopeptides in aqueous and physiological solutions, using MD simulations (GROMOS96), in nanosecond time scale simulations at pressure and temperature at normal conditions (P= 1bar,T= 300K). In aqueous solutions the SPC/E model is used, with null electric screening (k=0). For physiological solutions two methodologies are considered, a) with reaction field (RF) with electric screening, k=0,8 (inverse of Debye length value) and, b) with monovalent counter ions (CI) placed at substituted water positions, at physiological density conditions. The analysis of the root mean square RMSD departures of distances of the Ca-atoms compared with the NMR original conformation offered a good evaluation of the flexibility of the two biomolecules. In general, the mobility is higher both, for the residues located around the ends of the protein chain, and for the GLP-1. The averaged final conformations show that the peptides form alfa helixes in an aqueous and physiological media, in agreement with experimental data. Also the radius of gyration gave information about the evolution of the structure and dynamics of these hormones, suggesting that the molecular conformations were preserved as a whole. The existence of characteristic intra chain hydrogen bonds observed during the simulation stated the main role that can assigned to this type of interaction in preserving the stabilization of the structures. The water-water Hydrogen bond statistics also show that the presence of the two hormones strongly modify the H bonding pattern of SPC/E water as well as its dynamics. The comparison of results obtained from the different dynamics gives some hints for the comparison of methodologies for biomolecules in aqueous and physiological solutions. MCD and JRG are Members of Research Career of Comision de Investigaciones Cientificas de la Provincia de Buenos Aires-CIC and Consejo de Investigaciones Cientificas y Tecnicas -CONICET respectively, while SNM is a PHD applicant of FCE-UNLP. The authors gratefully acknowledge support to CONICET,CIC,UNLP and ANPCYT MCD and JRG are Members of Research Career of Comision de Investigaciones Cientificas de la Provincia de Buenos Aires-CIC and Consejo de Investigaciones Cientificas y Tecnicas -CONICET respectively, while SNM is a PHD applicant of FCE-UNLP. The authors gratefully acknowledge support to CONICET,CIC,UNLP and ANPCYT