Interaction between insulin receptor and a peptide derived from a trypsin inhibitor purified from tamarind seed: An in silico screening of insulin-like peptides

The aim of this study was to prospect in silico peptides derived from a multifunctional protein and assess their interaction with the insulin receptor (IR). The trypsin inhibitor isolated from tamarind seeds (TTI) was obtained through trypsin-sepharose 4B-CNBr affinity chromatography and subsequently characterized. The TTI underwent in vitro hydrolysis to assess its susceptibility to enzymatic degradation and determine suitable enzymes for cleavage in silico. The theoretical model was established to assess the purified tamarind seed trypsin inhibitor (TTIp 56/287) being cleaved in silico and selected for simulation by molecular dynamics. Among the peptides generated, Peptidetripquimo59 presented the most negative docking score (-175.53) with the IR, indicating strong affinity and stability in complex formation. Significant interaction with the IR was observed for key residues, including arginine 16 (-209.07 kJ mol-1), threonine 1 (-148.54 kJ mol-1), and valine 2 (-94.53 kJ mol-1). Additionally, it was discovered that both insulin and Peptidetripquimo59 exhibit binding to the identical location on the insulin receptor (IR). The results of the semi-empirical approach revealed that Peptidetripquimo59 exhibited greater potential for interaction with the IR compared to other complexes such as the insulin-IR complex, suggesting its candidacy as a starting point for the development of therapeutic agents targeting both type 1 and type 2 Diabetes mellitus.