Conglutins represent the major peanut allergens and are renowned for their resistance to gastro-intestinal digestion. Our aim was to characterize the digestion-resistant peptides (DRPs) of conglutins by biochemical and biophysical methods followed by a molecular dynamics simulation in order to better understand the molecular basis of food protein allergenicity. We have mapped proteolysis sites at the N- and C-termini and at a limited internal segment, while other potential proteolysis sites remained unaffected. Molecular dynamics simulation showed that proteolysis only occurred in the vibrant regions of the proteins. DRPs appeared to be conformationally stable as intact conglutins. Also, the overall secondary structure and IgE-binding potency of DRPs was comparable to that of intact conglutins. The stability of conglutins toward gastro-intestinal digestion, combined with the conformational stability of the resulting DRPs provide conditions for optimal exposure to the intestinal immune system, providing an explanation for the extraordinary allergenicity of peanut conglutins.

It has been demonstrated that sulfur–sulfur interactions can exist in various molecular systems. In this work we investigated sulfur–sulfur interactions in crystal structures of small molecules by analyzing geometric data from the Cambridge Structural Database (CSD) and by quantum chemical calculations. The analysis of cysteine residues (R-CH₂SH) in the crystal structures from the CSD indicates that in the sulfur–sulfur interactions the preferred is the parallel orientation of two C–S–H planes. Quantum chemical calculations were performed on model systems of methanethiol dimers. The most stable geometry of methanethiol dimer with parallel orientation of C–S–H planes is significantly strong; the interaction energy is −1.80 kcal/mol calculated at the very accurate CCSD(T)/CBS level. However, the strongest sulfur–sulfur interaction in methanethiol dimer (−2.20 kcal/mol) is the geometry with the σ-hole interaction, where the positive potential on one sulfur atom (σ-hole) interacts with negative potential on the sulfur atom of the second molecule. SAPT decomposition of the interaction energies was performed in order to explain the nature of the interactions. This study points out the importance of parallel interactions of cysteine residues and can be useful for recognizing the sulfur–sulfur interactions in the crystal structures and biomolecules.