Molecular dynamics simulations reveal that the immunogenic 33-mer peptides can adopt both folded and unfolded conformations

VIETRI AGUSTÍN; AMUNDARAIN MARÍA JULIA; DODERO VERONICA ISABEL; COSTABEL MARCELO DANIEL

Congreso; XLIX Reunión Anual SAB; 2021

Sociedad Argentina de Biofísica

The 33-mer peptide is an immunodominant fragment of α2-gliadin protein. It is found ingluten, and is proposed as the responsible of the immune response in celiac disease andother gluten-related disorders. This peptide is deamidated in the small intestine whichallows its recognition by the immune system, initiating the inflammation process. Bothpeptides are intrinsically disordered peptides (IDPs); this means that they do not have auniquely defined structure, which hampers a comprehensive description of their spatialconfiguration. Their structures have not yet been well characterized, so the aim of thiswork is to study the conformational landscape of wild-type and mutated peptides throughcomputational methods.Using GROMACS2020, 1.5 μs atomistic molecular dynamics simulations were performedto evaluate the conformational space of peptide 33-mer and its deamidated bioactiveform employing two force fields suitable for intrinsically disordered peptides, AMBER03wsand AMBER99-disp. In the present work the structures obtained from two different forcefields were assessed, evaluating on one hand, the possibility of using these force fieldswith these IDPs and, on the other hand, the structural differences due to the deamidation.In general, both peptides show a preference for extended conformations. However, the33-mer peptide adopts more folded structures than the deamidated one. The trajectorieswith both force fields describe similar regions of the conformational landscape, buthistograms of Ramachandran plots show more content of polyproline II secondarystructure when using AMBER99-disp force field. The structures obtained for the peptidesfrom both force fields are suitable for examining their aggregation.