Computational evaluation of the first oligomers formed in the auto-aggregation process of 33-mer peptide.

MARÍA J. AMUNDARAIN; FERNANDO ZAMARREÑO; JUAN FRANCISCO VISO; VERÓNICA DODERO; MARCELO D. COSTABEL

Caxambú

Otro; Reunión Anual de la Federación de Sociedades de Biología Experimental.; 2014

Federación de Sociedades de Biología Experimental.

Celiac disease is an autoimmune disorder characterized by the damage of the epithelial cells of the small intestine caused by an inflammatory process as a response to the ingestion of gluten-containing food. Gluten is a proteic complexpresent in wheat, barley and rye [1] which contains different proteins belonging to the Gliadin and Glutein families. Studies have revealed that a 33-residue fragment of the alfa2-gliadin (representative of the family) has an unusualresistance towards digestion. This fragment, called 33-mer, presents three T-cell epitopes previously identified in celiac patients [2]. The combination of its metabolic stability and multivalence are hints that allow us to propose it as apotential toxic agent for the small intestine cells; and therefore it is the object of study of this work. In vitro studies of the 33-mer, whose sequence is LQLQPF(PQPQLPY)3PQPQPF, revealed that its secondary structure is mainly PPII helix[3]. In addition, works that include circular dichroism and electronic microscopy suggest a tendency towards aggregation in a concentration-dependent manner.[4]Molecular modelling methods represent essential tools to undertake the study of biological systems, providing a better understanding of both their structure and functionality. In this work we applied molecular dynamics simulations andelectrostatic calculations to analyse the initial steps of auto-aggregation of 33-mer peptide.