STRUCTURE PREDICTION AND IN-SILICO DESIGNING OF DRUGS AGAINST PLANT HEMEODOMAIN FINGER PROTEIN 14 FOR SUPPRESSION OF MALIGANT TRANSFORMATION AND TUMORIGENICITY OF NON SMALL CELL LUNG CANCER
Technical advancement of the invention as compared to the existing knowledge: > Plant Homeodomain Finger Protein 14 (PHF14) might be involved in the development of lung cancer and plays a significant promoting role in eel] proliferation of different cell lines. As per today the experimental techniques fail to precisely define the 3-Dimensional structure of PHF14 in this work, an in-silico model of PHF14 protein (Figure 1) 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 Drugbank, and were docked against PHF14 protein using online server Patchdock. The structure of ligand DB08438 with the maximum score was varied by using ACD/ChemSketch 8.0 and the docking was done for the resulting 22 new ligands. The results indicated that in-silico docking of selected ligands, i.e., Iigandsl2-16, 18-23, 26, 29-33, with PHF14 protein exhibited favorable binding interactions as compared to that of ligand DB08438, while the ligand31 (Figure 4) [(2Z)-6- 0-(7,11,15-trioxohexadecanoyl)-L-threo-hex-2-enonic acid] bears the maximum score of 6660 with the target protein and thus the prospects oi binding of ligand31 with the PHF14 are high. Principal use of the invention: > It is a well-known fact that the function of the protein critically depends upon its structure. As the present experimental techniques fails to correctly elucidate the structure of PHF14 protein, this invention provides the validated homology modeled PHF14 protein structure. > The in silico molecular docking studies of selected ligand31 with PHF14 protein exhibited favorable binding interactions and warranted further studies for. the development of potent inhibitors for the over expression of PHF14 protein for the suppression of malignant transformation and tumorigenicity oi non small cell lung cancer
