Published online Apr 7, 2014. doi: 10.3748/wjg.v20.i13.3401
Revised: January 6, 2014
Accepted: March 6, 2014
Published online: April 7, 2014
Processing time: 188 Days and 16.6 Hours
Hepatitis C virus (HCV) helicase is a molecular motor that splits nucleic acid duplex structures during viral replication, therefore representing a promising target for antiviral treatment. Hence, a detailed understanding of the mechanism by which it operates would facilitate the development of efficient drug-assisted therapies aiming to inhibit helicase activity. Despite extensive investigations performed in the past, a thorough understanding of the activity of this important protein was lacking since the underlying internal conformational motions could not be resolved. Here we review investigations that have been previously performed by us for HCV helicase. Using methods of structure-based computational modelling it became possible to follow entire operation cycles of this motor protein in structurally resolved simulations and uncover the mechanism by which it moves along the nucleic acid and accomplishes strand separation. We also discuss observations from that study in the light of recent experimental studies that confirm our findings.
Core tip: Proteins that are involved in the replication cycle of hepatitis C virus are relevant targets for antiviral therapies. Their dynamical properties, however, cannot be sufficiently studied in experiments yet. Alternatively, owing to the available power of modern computers, the mechanism by which they operate can be investigated in computer experiments using appropriate models. In this regard, considerable progress has now been achieved for the viral helicase protein and the obtained results, in combination with experimental data, have significantly improved our understanding of its activity.