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

MARÍA JULIA AMUNDARAIN; FERNANDO ZAMARREÑO; JUAN FRANCISCO VISO; VERONICA DODERO; MARCELO DANIEL COSTABEL

Caxambu

Congreso; XXIX reunion anual de la federación de sociedad de biología experimental; 2014

Universidad de Sao Pablo

Coeliac disease is an autoimmune disorder that produces lesions in the small intestine. It is triggered by the ingestion of gluten, a protein complex found in wheat, rye and barley. It has been published that the 33-mer peptide, a fragment found after partial degradation of the protein α2-gliadin, is highly resistant to digestion and shows three T-cell epitopes previously identified in patients. It has been proposed that this peptide, LQLQPF(PQPQLPY)3PQPQPF, initiates the inflammation process that leads to the damage of the epithelial cells of the small intestine. However, the molecular bases of the process are not yet fully understood. We are particularly interested in studying its ability of auto-aggregation into more complex structures, since different superstructures have been observed in vitro. 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 and electrostatic calculations to analyse the initial steps of auto-aggregation of 33-mer peptide. As a starting point we used GROMACS package to carry out a molecular dynamics simulation of the monomer, in water for 50 ns, to assess its behaviour. In order to evaluate the aggregation process we first performed an electrostatic energy calculation, using APBS, on different configurations that might lead to the formation of a dimer and a trimer. For both oligomers, we calculated the electrostatic energy of interaction and chose the systems with the most negative energy to perform molecular dynamics simulations (again of 50 ns each). We found that the formation of dimers and trimers is statistically possible, and its structural characteristics are consistent with experimental data available.