Molecular docking of human ABCC2/MRP2 efflux pump inhibitors

Abstract

    ABCC2/MRP2 is a member of ATP-binding cassette family of transporters. This efflux transporter is found in the apical membranes of polarized cells and is expressed mainly in the liver, kidney and intestine. ABCC2 involves in absorption, distribution and excretion of drugs and xenobiotics. Overexpression of this pump also contributes to the drug resistance of cancer cells. In this thesis, molecular docking on ABCC2 inhibitors have been developed. These models are aimed to identify the residues making contact with ABCC2 inhibitors and to establish a computational prediction model on ABCC2 inhibitors. FlexX tool integrated in Lead IT was used for molecular docking studies of 204 ABCC2 inhibitors. 3D structure of ABCC2 pump has been predicted by I-Tasser online server. For molecular docking, amino acid played an important roles in central cavity was Arg943, Arg943 was identified to bind with majority of ligands by 2 hydrogen bonds and 1 hydrophobic interaction. ABCC2 homology was successfully developed with good quality and high confidence by I-Tasser server. This 3D-structure homology was used to built molecular docking model at central cavity in order to find out important residues and bonds.