Ensemble Pharmacophore Meets Molecular Docking: A Novel Screening Approach for the Identification of B-Raf Kinase Inhibitors

In US about 106110 diagnosed as melanomas, 7,180 people expected to die due melanoma. B-RAF is a cytoplasmic serine - threonine kinase that found in mutated form melanoma and colorectal cancer. Sorafenib was initially introduced inhibitor Hence it taken pivot molecule our study. Four potent B-Raf inhibitors (Sorafenib, Regorafenib, N-desmethyl sorafenib & Donafenib) are used build pharmacophore model with ‘PharmaGist webserver’ which generated 5-point hypothesis. The best score of 27.780, screen the Zinc database ZINCPharmer web server obtain similar hits. By applying filters like Lipinski rule, RMSD criteria top ten hits were identified. Subsequently, molecular docking performed on wild (1UWH) (3IDP) protein targets by using GLIDE 5.6 (Schrödinger), prioritize lead molecules. Further these molecules subjected ADME Properties Prediction Qik Prop module. Among ten, nine have glide scores range nearer standard i.e., Sorafenib. Finally, we conclude ZINC02853810 may act powerful against both mutant type has highest than Standard. 
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