Mohammed Ahmed Mohammed Mansour
Tanta University, Egypt
Title: Molecular docking of potent inhibitors of oncoproteins using Swiss dock and visualization by UCSF chimera
Biography
Biography: Mohammed Ahmed Mohammed Mansour
Abstract
Histone deacetylases (HDACs) play critical roles in apoptosis and contribute to the proliferation of cancer cells. AR-42 is a novel Class I and II HDAC inhibitor that shows cytotoxicity against multiple human cancer cell lines. Recently, it was reported that AR-42 inhibits the activity of HDAC5 in hepatocellular carcinoma (HCC). However, the binding mode of action and molecular docking of this inhibitor is not reported. This study aims to evaluate the possible therapeutic efficacy of this inhibitor by testing its docking with different targets of HDACs. HDAC5 was found to be upregulated in HCC tissues compared to adjacent normal tissues, and this was correlated with reduced patient survival. Treatment with AR-42 decreased HCC cell growth and increased caspase-dependent apoptosis, and this was rescued by HDAC5 overexpression. We demonstrated that AR-42 can inhibit the deacetylation activity of HDAC5 by assessing the docking using Swiss dock software. SwissDock is a web service to predict the molecular interactions that may occur between a target protein and a small molecule. Then, we visualized our docking results using UCSF Chimera, a highly extensible, interactive molecular visualization and analysis system. Chimera can read molecular structures and associated data in a large number of formats, display the structures in a variety of representations, and generate highquality images and animations. Taken together, these results demonstrate for the first time that AR-42 targets HDAC5 and induces its inhibition in human hepatocellular carcinoma. AR-42 therefore shows potential as a new drug candidate for HCC therapy.