Molecular Dynamics of Non-Structural Proteins of Hepatitis C Virus.

      Аннотация: There are no vaccines available against HCV and existing therapy with pegylated interferon-? and ribavirin shows only 50% efficiency. It is expensive and poorly tolerated. The non-structural protein of HCV (NS5B) is thought to be responsible for replication of the viral genome. The nucleotide drug sofosbuvir is also approved for combinational treatment of chronic HCV. For the development of new non-nucleotide inhibitors it is necessary to catalogue all the available and experimentally tested drugs along with their IC50 values. Here, the most active drugs are filtered and their structures are compared. Their docking at the active site and the interaction with the amino acids are mapped with their ability in in vitro and in vivo experiments. The MD simulation studies and calculation of binding free energies estimates the stability of inhibitors in the complex. The decomposition energy studies predict the amino acids which are playing significant role in the binding of drugs that are verified by mutational studies. In search of new drugs my studies can also be helpful in developing effective drugs; that will be more active and inhibit the functions of HCV.

Ключевые слова: Ab intio calculations, MD simulations, Free energy calculations, Molecular Docking, Protein-ligand interactions, Hepatitis C virus, Qm/MM Calculation