Protein-dynamics of the putative HCV receptor CD81 large extracellular loop

The human CD81 protein is a likely receptor for the binding of hepatitis C virus (HCV) to hepatocytes and therefore a possible target for novel anti-HCV drugs. The two published X-ray structures of the HCV binding region of CD81 (1G8Q and 1IV5) have, particularly in a substructure that is formed by two helices, a slightly different conformation. The abovementioned substructure is a candidate target region for virtual screening approaches. We present here a molecular dynamics study of the two X-ray structures. Our results indicate that the conformation of the two helical regions in one of the X-ray structures (1G8Q) is affected by crystallographic contacts and most likely does not represent the native state of the protein.