Structure Prediction and In-Silico Designing of Drugs against Fork head-Box R2 Protein

Abstract

Forkhead-box (FOX) family proteins, involved in cell growth and differentiation as well as embryogenesis and longevity, are DNA-binding proteins regulating transcription and DNA repair. Objective: FOXR2 promotes cell proliferation and malignancy in hepatocellular carcinoma (HCC) and could be a novel promising therapeutic target for this disease. Methods: In this work, an in-silico model of FOXR2 protein was generated using the approach of homology modeling and loop modeling. The model was validated with Ramachandran plot analysis. The ligands were generated with the help of Drug bank, ZINC data base, and Kegg data base and were docked against FOXR2 protein using online server Patchdock. The structure of ligand ZINC 3830634 with the maximum score was varied by using ACD/ChemSketch 8.0 and the docking was done for the resulting 10 new ligands. Results and Conclusion: The results indicated that the designed ligands 3 and 10 shows better docking score than that showed by ZINC 3830634. Thus, justifies further studies needed for the development of potent inhibitors for the over expression of FOXR2 protein making the management of HCC more efficient.