Inhibitory Potential of a Designed Peptide Inhibitor Based on Zymogen Structure of Trypsin from Spodoptera frugiperda : In Silico Insights

Spodoptera frugiperda (J.E. Smith) is an invasive pest in agriculture. It can potentially damage yield resulting severe crop losses and subsequently significant economic damage each year. S. frugiperda is predominantly managed using traditional chemical pesticides. Accordingly, sustainable alternatives such as digestive enzymes inhibitors can be used as an efficient pest management that protects the environment. This contribution aims to examine the pro-region of S. frugiperda trypsin as specific inhibitor of the pest protease enzyme. Structural modeling in conjunction with molecular docking simulations were conducted to design a peptide sequence with the best docking scores and strong binding energy to the target enzyme. The structural models of six pro-peptides were produced based on modification of 7-amino acids of the pro-region of S. frugiperda trypsin. VERIFY_3D, ERRAT, PROCHECK, PROSA and WHAT-IF scores validated the reliability of the predicted model of S. frugiperda trypsin. Molecular docking studies between the six designed inhibitor peptides and the predicted model structure at three different pH conditions were carried out. Data revealed that VPSNPQR at pH 11.0 with the best docking score, the lowest binding energy (ΔG) and dissociation constant (Kd) indicated a potent binding affinity towards S. frugiperda trypsin’s active site. Moreover, the peptide showed a weak potential for interaction with the human trypsin. The results indicated the importance of computational studies in design and selection of inhibitor peptides against target enzymes. Such inhibitors can be used for S. frugiperda control, which can be further applied in other pest management programs. Docking simulations between the pro-peptide inhibitor and Spodoptera frugiperda midgut trypsin confirmed the capacity of the designed pro-region in inhibiting the insect trypsin.