Computational profiling and rational design of peptide inhibitors targeting trypsin in Helicoverpa armigera (Hübner): A structure-based approach

This study computationally evaluates the inhibitory potential of peptides derived from protease pro-regions and naturally occurring protease inhibitors against Helicoverpa armigera trypsin, a key digestive enzyme in this major agricultural pest. A computationally generated peptide library, sourced from protease pro-regions and natural inhibitors across insect species, was screened using consensus docking, molecular dynamics (MD) simulations, Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) calculations, binding pattern analysis, and physicochemical characterization. Among the screened peptides, three novel sequences (PRALHRV, GFLRNGE, and PKTRICT) together with a native peptide (VPKSVNR) showed favorable docking scores and interaction patterns with key catalytic residues of trypsin (H68 and D113). Molecular dynamics simulations were subsequently performed to assess the stability of the peptide–enzyme complexes under simulated alkaline midgut conditions. Furthermore, assessment of structural flexibility and isoelectric points (pI) predicted that both peptides remain stable under the alkaline conditions of the insect gut. Predicted cross-reactivity with trypsin-like enzymes in other pest species also suggests potential for broad-spectrum application. This study computationally assessed PRALHRV and VPKSVNR as potential peptide-based inhibitors of H. armigera trypsin, providing a foundation for pending experimental validation and future development. These results provide computational insights into possible peptide–trypsin interaction motifs and showed candidate sequences that may warrant further investigation. The proposed computational framework may assist future efforts aimed at identifying peptide candidates targeting digestive proteases in H. armigera. With appropriate experimental validation, such peptides could potentially contribute to the development of novel pest management strategies, including peptide-based bioinsecticides or transgenic crop protection approaches. These findings may therefore provide a preliminary basis for future studies exploring enzyme-specific inhibitors as part of environmentally sustainable pest control strategies.