Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery: Bridging Experiments and Computations - September 10-14, 2014, Istanbul, Turkey

Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery Poster Session I

23-POS Board 23 Structural Analysis of Putative HCV Glycoprotein E2 Binding Sites on Human CD81 in Compared with Their Mouse Counterparts Chun-Chun Chang 1,2 , Hao-Jen Hsu 3 , Je-Wen Liou 1 . 1 Department of Medical Sciences, Tzu Chi University, Hualien City, Taiwan, 2 Departments of Laboratory Medicine, Buddhist Tzu Chi General Hospital, Hualien City, Taiwan, 3 Department of Life Sciences, Tzu Chi University, Hualien City, Taiwan. Hepatitis C virus (HCV), formally identified in 1989, is an enveloped virus with a single positive stranded genomic RNA. HCV infection in patients often results in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. However, the treatments for HVC infection are still limited. This might be due to the fact that the current cell and animal model systems are not sufficient for studying the HCV infection in details. In this study, we are firstly aiming to investigate the interactions between HCV E2 protein and CD81 of host cells, which have been proved crucial for HCV entry into host cells, using molecular docking. From the bioinformatic results, we should be able to develop the potential peptide drugs for interrupting HCV E2/CD81 interactions to prevent the HCV infection into host cells. Previous studies showed that HCV can bind to human CD81 with high specificity. For comparison, homology modeling was also performed to obtain the structure of mouse CD81 using human CD81 as a template with high similarity up to 93%. So far, the docking results showed that the short helices near C-terminal domain of HCV E2 bind to the head regions of dimeric human CD81 with hydrophobic contacts, while the binding sites are altered when the HCV E2 are docked to mouse CD81. Two peptides were designed based on the docking prediction and the work were followed by the synthesis of fluorescent dye 5-carboxyfluorescein labelled peptides and flow cytometry in order to measure the binding efficiency of the synthetic peptides onto host cells.

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