Molecular Docking studies reveals Rhein from rhubarb (Rheum rhabarbarum) as a putative inhibitor of ATP-binding Cassette Super Family G member 2.

ATP-binding cassette super family G2 protein is an active ATP-binding cassette transporter with potential to combat cancer stem cells.Due to the lack of potential ATP-binding cassette super family G2 inhibitors we screened natural inhibitors, which could be safe source to control multidrug resistance by blocking the regulation of ATP-binding cassette super family G2 protein.Three-dimensional structure of ATP-binding cassette super family G2 protein downloaded from the protein databank and chemical structures of selected 166 compounds of the training dataset retrieved from PubChem. Drug-likeness and docking analysis shortlisted the dataset for pharmacophore generation. LigandScout 4.1.5 used for pharmacophore-based screening of Zbc library of ZINC database and Autodock Vina utilized for molecular docking against the predicted active pocket of the target protein to evaluate potential association of protein and ligands. Physiochemical properties of novel compounds calculated by admetSAR respectively.Through pharmacophore-based screening, ZINC4098704 (Rhein) was identified as a lead compound which demonstrates least binding energy (-8.5) and highest binding affinity with the target protein and showed optimal physiochemical profile. This compound is highly recommended for laboratory test to confirm its activity as ATP-binding cassette super family G2 inhibitors.Our computer-based study systematically selected natural lead compound, which could be effective in inhibiting ATP-binding cassette super family G2 and may be helpful in reversing the effect of multidrug resistance in order to increase the effectiveness of chemotherapy in cancer treatment.