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Analysis of the Resistance of Hepatitis C Virus NS5B Polymerase Inhibitors via Docking and Molecular Dynamics Simulation
Author(s) -
Uengwetwanit Tanaporn,
Robaa Dina,
Sippl Wolfgang
Publication year - 2015
Publication title -
molecular informatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.481
H-Index - 68
eISSN - 1868-1751
pISSN - 1868-1743
DOI - 10.1002/minf.201400048
Subject(s) - ns5b , docking (animal) , mutant , molecular dynamics , enzyme , chemistry , benzimidazole , polymerase , hepatitis c virus , biochemistry , stereochemistry , virology , biology , virus , computational chemistry , hepacivirus , gene , medicine , nursing , organic chemistry
In this work, we examined how known single point mutations (P495S, P495L, P495A, P496A, P496S and V499A) in Hepatitis C virus NS5B polymerase influence the binding of benzimidazole‐5‐carboxamide derivatives which are potent NS5B inhibitors. Docking and molecular dynamics simulations were performed to analyze the binding of the inhibitors to the wild‐type and mutant enzymes. Binding free energy calculations (MM‐GB/SA method) and analyzing the decomposed binding free energy of individual residues were able to explain the differences in the inhibitory potency of the compounds at wild‐type and mutant enzymes and hence account for the appearance of resistance of mutant enzymes to the studied inhibitors. The obtained results were found to be in agreement with the known experimental data.