In silico methods to identify meat-derived prolyl endopeptidase inhibitors

According to the World Health Organization (WHO), approximately 450 million people suffer from mental or neurological disorders and five of the ten leading causes of disability and premature death worldwide are psychiatric conditions. Social, biological and neurological sciences provided extensive understanding into the role of risk and protective factors in the development of mental disorders and poor mental health. Altered activity of a number of enzymes, such as prolyl endopeptidase (PEP, EC 3.4.21.26), has been linked to the prevention and treatment of a number of mental disorders, including anxiety, depression and Alzheimer's disease. The inhibition of PEP has potential for use in the prevention and in the treatment of mental disorders. The objective of this work was to identify PEP-inhibitory peptides from meat proteins using in silico methods. In this paper, five proteins commonly found in meat by-products were evaluated as a substrate for use in the generation of PEP inhibitory peptides. These include serum albumin, collagen and myosin. These proteins were cleaved in silica using BIOPEP and ExPASy PeptideCutter and the generated peptides were compared to known PEP-inhibiting peptides in the database of BIOPEP. A number of novel PEP inhibitory peptide sequences were identified in this study, including PPL, APPH, IPP and PPG with corresponding IC50 values of 2.86, 3.95, 4.02 and 2.70 mM, respectively. This work demonstrates the usefulness of in silico analysis for predicting the release of PEP-inhibiting peptides from meat proteins. (c) 2014 Elsevier Ltd. All rights reserved.