Conformational and docking analyses of the frenatin 3 peptide, an inhibitor of nNOS enzyme and a ligand for Ca2+-calmodulin

Abstract

The bioactive peptides are one of the promising drugs to curb a number of diseases. Recently, eighty peptide based drugs have been approved by Food and Drug Administration. The skin peptides of frogs have been studied for their activities in large number of cellular and biomolecular processes i.e., up regulation, down regulation and inhibition. The frenatin 3 peptide, from the skin of Litoria infrafrenata, has been studied for conformation and secondary structure elements. The simulation studies have been carried out for frenatin 3 peptide and its computational mutants. The results suggested the most populated secondary structural elements, their stability and also reflect the effect of mutations on structure. Further, the docking studies with known targets of frenatin 3 were revealed the peptide-protein interactions i.e., backbone-backbone, side chain – side chain and backbone – side chain. The hydrophobic core formed by EF hand motif of calmodulin plays very important role in peptide-calmodulin interactions. The inhibition of Ca2+-calmodulin complex by frenatin 3 peptide, consequently the inhibition of nNOS synthase, predicted to occur from molecular docking studies. The peptide-protein hydrophobic interactions considered to be the main player in this case. The homology and immunoinformatic studies on these peptides were performed to test their immunological role and thus proposed for further experimental studies.