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

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.