Statistical modelling of in vitro pepsinolysis using peptidomic data
Résumé
Proteins digestion is a complex and dynamic process involving several proteases that particularlydiffer in their specificity. The specificity of pepsin, the major protease of gastric digestion, has beenpreviouslyinvestigated,butonlyregardingtheprimarysequenceoftheproteinsubstrates. Thepresent study aimed to consider in addition physicochemical and structural characteristics, at themolecular and sub-molecular scales. For six different proteins submitted to in vitro gastric digestion,the peptide bonds cleaved were determined from the peptides released and identified by LC-MS/MS.An original statistical approach, based on propensity scores calculated for each amino acid residue onboth sides of the peptide bonds, concluded that preferential cleavage occurred after Leu and Phe, andbefore Ile. Moreover, reliable statistical models developed for predicting peptide bond cleavage,highlighted the predominant role of the amino acid residues at the N-terminal side of the peptidebonds,up to the seventh position (P7 and P7’). The significantinfluence ofhydrophobicity, chargeandstructuralconstraintsaround the peptidebonds wasalsoevidenced.