Binding sensitivity of adefovir to the polymerase from different genotypes of HBV: molecular modeling, docking and dynamics simulation studies.

ABSTRACT:

Aim

To investigate the molecular mechanisms underlying the influence of DNA polymerase from different genotypes of hepatitis B virus (HBV) on the binding affinity of adefovir (ADV).

Methods

Computational approaches, including homology modeling, docking, MD simulation and MM/PBSA free energy analyses were used.

Results

Sequence analyses revealed that residue 238 near the binding pocket was not only a polymorphic site but also a genotype-specific site (His238 in genotype B; Asn238 in genotype C). The calculated binding free-energy supported the hypothesis that the polymerase from HBV genotype C was more sensitive to ADV than that from genotype B. By using MD simulation trajectory analysis, binding free energy decomposition and alanine scanning, some energy variation in

SUBMITTER: Li J 

PROVIDER: S-EPMC4011611 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature