Modeling of biopeptides in physiological solutions Molecular dynamics simulation, Conferencia invitada XV

MC DONNAMARIA; M. PAULINO ZUNINI; R CARRARO; SN MONACHESI; Z CATALDI; F LAGE

Mar del Plata, Argentina

Conferencia; Conference on Nonequilibrium Sattistical Mechanics and Nonlinear Physics, MEDYFINOL06; 2006

Facultad de Ingenieria, UNMDP(Argentina), Facultad de Ingenieria, Univ. de los Andres (Chile), FCEN-UBA (Argentina)

More than 30 year have passed since the initial discoveries o bioactive peptides in tissues from vertebrate an invertebrate non-mammalian species. Exendin-4 (EX4),.a natural, 39-residue peptide, first isolated from the salivary secretions (venom) of Gila Monster, and glucagon-like peptide-1,(GLP-1,30–aminoacids) which is a mammalian hormone, possess a remarkable aminoacid sequence homology, and bind to the same G-protein coupled receptor. Both neuroendocrine hormones are being investigated as potential therapeutic agents for treatment of diabetes and obesity due to their glucoregulatory actions. 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 physiological solutions, a) with reaction field and electric screening , b) with counterion dynamics, using molecular dynamics simulations (GROMOS96) during 3ns. The flexibility is measured through the root mean square departures of distances of the C-atoms compared with the NMR original experimental conformation. 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 physiological media, in agreement with experimental data. Furthermore, the existence of some intra chain hydrogen bonds could also contribute to stabilize the helix structures. The water-water Hydrogen bond statistics shows that the presence of the two hormones disturb the H bonding pattern of SPC/E water as well as its dynamics, producing an increasing in the water bonded molecules which indicates some hydrophobic character of the peptides. The comparison of results obtained from the two dynamics gives some hints for the comparison of methods.