PERSONAL DE APOYO
VISO Juan Francisco
congresos y reuniones científicas
Título:
Computational evaluation of the first oligomers formed in the auto-aggregation process of 33- mer peptide
Autor/es:
MARÍA JULIA AMUNDARAIN; FERNANDO ZAMARREÑO; JUAN FRANCISCO VISO; VERONICA DODERO; MARCELO DANIEL COSTABEL
Lugar:
Caxambu
Reunión:
Congreso; XXIX reunion anual de la federación de sociedad de biología experimental; 2014
Institución organizadora:
Universidad de Sao Pablo
Resumen:
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.