In silico studies on the interaction of phage displayed biorecognition element (TFQAFDLSPFPS) with the structural...

White spot disease caused by the white spot syndrome virus (WSSV) incurs a huge loss to the shrimp farming industry. Since no effective therapeutic measures are available, early detection and prevention of the disease are indispensable. Towards this goal, we previously identified a 12-mer phage displayed peptide (designated as pep28) with high affinity for VP28, the structural protein of the white spot syndrome virus (WSSV). The peptide pep28 was successfully used as a biorecognition probe in the lateral flow assay developed for rapid, on-site detection of WSSV. To unravel the structural determinants for the selective binding between VP28 and pep28, we used bioinformatics, structural modeling, protein-protein docking, and binding-free energy studies. We performed atomistic molecular dynamics simulations of pep28-pIII model totaling 300 ns timescale. The most representative pep28-pIII structure from the simulation was used for docking with the crystal structure of VP28. Our results reveal that pep28 binds in a surface groove of the monomeric VP28 β-barrel and makes several hydrogen bonds and non-polar interactions. Ensemble-based binding-free energy studies reveal that the binding is dominated by non-polar interactions. Our studies provide molecular level insights into the binding mechanism of pep28 with VP28, which explain why the peptide is selective and can assist in modifying pep28 for its practical use, both as a biorecognition probe and a therapeutic.