Recognition and stabilization of a unique CPRI - Structural motif in Cucurbitaceae family trypsin inhibitor peptides: Molecular dynamics based homology modeling using the X-ray structure of MCTI-II

The high resolution crystallographic structure of MCTI-II complexed with be ta trypsin (PDB entry 1 MCT) was used to model the corresponding structures of the six inhibitor peptides belonging to Cucurbitaceae family (MCTI-I, L A-1, LA-2, CMTI-I, CMTI-III, CMTI-IV). Two model inhibitors, LA-1 and LA-2 were refined by molecular dynamics to estimate the average solution structu re. The difference accessible surface area (DASA) study of the inhibitors w ith and without trypsin revealed the Arginine and other residues of the inh ibitors which bind to trypsin. The hydration dynamics study of LA 1 and LA2 also confirm the suitability of water molecules at the active Arg site. Mo reover, the presence of a unique 3D-structural motif comprises with the fou r CPRI residues from the amino terminal is thought to be conserved in all t he six studied inhibitors, which seems essential for the directional fixati on for proper complexation of the Arg (5) residue towards the trypsin S1-bi nding pocket. The role of the disulphide linkage in the geometrical stabili zation of CPRI (Cysteine, Proline, Arginine, Isoleucine) motif has also bee n envisaged from the comparative higher intra molecular Cys (3) -Cys (20) d isulphide dihedral energies.