科研之友
微信
新浪微博
Facebook
分享链接
摘要
Hepatitis B virus (HBV) is the most common cause of liver infection. This can be treated by targeting HBV DNA polymerase (HDP). Although many drugs are available for the treatment, lamivudine is widely used because of its good safety profiles. Lamivudine targets the reverse transcriptase activity of HDP and restricts the viral growth. However, the available literature evidence showed that the mutations in the catalytic site of tyrosine (Y203), methionine (M204), aspartic acid (D205) and aspartic acid (D206) will significantly reduce the efficacy of lamivudine and creates a resistance. In particular, M204V mutation affects the drug binding mechanism and cause resistance to lamivudine. Therefore, in the present study, we made an attempt to understand the mechanism of lamivudine resistance with the aid of computational techniques. The docking results suggest that lamivudine was found to adopt most promising conformations with native type HDP by identifying M204 as a prospective partner for making polar contacts as compared to the mutant type HDP. The molecular dynamic (MD) results showed that the average atom, especially atoms of the native-type HDP-lamivudine complex, movements were small, displayed fast convergence of energy and charges in geometry. This highlights the stable binding of the lamivudine with native-type HDP as compared to mutant type HDP. The normalized mean square displacement and root mean square fluctuation analysis certainly indicates conformational changes in the HDP structure due to M204V mutation. Furthermore, the hydrogen bond analysis from the MD study demonstrated that there is decreased number of intermolecular hydrogen bonds in mutant HDP-lamivudine complex than that in the native-type HDP-lamivudine complex.
- 出版日期2014-11
