In silico investigation of pro-peptides from insect zymogens as mimetic inhibitors for digestive chymotrypsin of beet armyworm, Spodoptera exigua

Spodoptera exigua (Hübner), a highly destructive pest of agricultural crops, is often managed through the use of chemical pesticides. However, the use of chemical pesticides can have negative impacts on human health and the environment, making it important to find sustainable and alternative approaches to effectively manage this pest. One promising solution is the use of inhibitors that hinder the activity of proteases in the insect's digestive tract. Many digestive proteases, such as chymotrypsin, are produced as inactive zymogens with N-terminal pro-regions, which act as intramolecular chaperones and inhibitors of cognate catalytic regions. The present study aimed to utilize various bioinformatics tools to identify the physicochemical properties, secondary structures, and topology of chymotrypsin from S. exigua. Furthermore, we evaluated the potential of peptide inhibitors derived from the pro-region of zymogens that could be utilized as mimetic inhibitors for chymotrypsin in S. exigua. Homology molecular modeling was performed using SWISS-MODEL, and the validation of the predicted model was done by various programs. Molecular docking studies between five homologous species-derived protease inhibitors and the predicted model following by molecular dynamics (MD) simulation coupled with Molecular Mechanics Poisson–Boltzmann Surface Area (MMPBSA) calculations were also applied and the analysis of peptides/enzyme interactions revealed the antagonistic capacity of two screened inhibitors against S. exigua chymotrypsin. Protein-protein interaction networks demonstrated that chymotrypsin from S. exigua interacted with eleven other proteins in a high confidence score. Active site analysis revealed that S219, D230, and H232 serve as catalytic residues. These findings demonstrate a central role for computational methods in designing a potent inhibitor peptide that is highly specific and selective to its mature enzyme. Our study could be promising for future insecticide designs used in S. exigua control.