Exploring STAT3 stimulatory potential of novel wound healing molecules by virtual screening and molecular dynamics simulations.

STAT3 signaling is a major intrinsic pathway for cell proliferation owing to its frequent activation in injured tissues. Various STAT3-regulated genes encode cytokines and growth factors, the receptors of which in turn activate the same STAT3 pathways, thereby regulating cell proliferation. In present study, we aimed to analyze several compounds for their wound healing and tissue repair potential by computer-aided virtual screening and Molecular dynamics (MD) simulation. Based on literature studies, a total of 36 drug molecules were selected having critical functions in wound healing and tissue repair. The pharmacological features (ADME and toxicity) of these molecules were predicted to find lead molecules among them. Further, a comparative study was performed to screen binding efficiency of STAT3 with many conventional wound healers by molecular docking. Among all, W6S, Strychnin, Prednisone and N-(6-(4-(3-(4-((4-Methylpiperazin-1-yl) methyl)-3- (trifluoromethyl)phenyl)ureido)phenoxy)pyrimidin-4-yl)cyclopropanecarboxamide showed best docking with STAT3 protein. The calculated binding energy of these molecules with STAT3 was found to be -8.9 Kca/mol for N-(6-(4-(3-(4-((4-Methylpiperazin-1-yl) methyl)-3-(trifluoromethyl) phenyl)ureido)phenoxy)pyrimidin-4-yl)cyclopropanecarboxamide, -8.7 Kcal/mol for W6S, -8.5 Kcal/mol for Strychnine and -8.4 Kcal/mol for Prednisone . The result was reconsidered for MD simulation. The simulation result showed stable binding of the ligand with STAT3 protein for 100 ns. These compounds showed better interaction potential with STAT3 was compared to known tissue repair molecules. Our data paves way for further exploration of these molecules as novel cell proliferators to be tested in various types of wound and tissue injuries.Communicated by Ramaswamy H. Sarma.