Model based design of inhibitors for c-jun.

Literature shows that various molecular cascades are activated by stress, UV rays and pollutants leading to wrinkle formation of the skin. These cascades start from five types of receptors (EGFR, PDGFR, PAFR, IL1R, TNFRB) and terminate with the production of matrix metalloproteinase's, which degrades collagen leading to wrinkle formation. Signaling pathway leading to wrinkle formation showed that c-jun is involved in these cascades. Therefore, c-jun is the preferential choice for inhibition to reduce the intensity of collagen degradation. Hence, the 3D structure of c-jun was modeled using segment based homology modeling by MODELLER 9v5. Evaluation of the constructed model was done by PROCHECK, WHAT CHECK and through RMSD/RMSF calculations. Ligands for the inhibitory sites were designed using LIGANDSCOUT. The interaction study of ligand and receptor was performed by AUTODOCK. A library of analogues was constructed for three known inhibitory sites. The receptor-analogue study was performed using the software MOLEGRO Virtual Docker. The analogues constructed from the designed novel reference ligands showed good binding with the receptor binding sites. It should be noted that these predicted data should be validated using suitable assays for further consideration.