Understanding the unique mechanism of l-FMAU (Clevudine) against hepatitis B virus: molecular dynamics studies

• Published in: Bioorganic & medicinal chemistry letters Vol. 12; no. 23; pp. 3459 - 3462
• Main Authors: Chong, Youhoon, Chu, Chung K
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 02.12.2002; Elsevier
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Arabinofuranosyluracil - analogs & derivatives; Arabinofuranosyluracil - chemistry; Arabinofuranosyluracil - pharmacology; Binding Sites; Biological and medical sciences; Computer Simulation; Databases, Factual; DNA Replication - drug effects; Hepatitis B virus - drug effects; Hepatitis B virus - enzymology; Medical sciences; Models, Molecular; Nucleic Acid Synthesis Inhibitors; Pharmacology. Drug treatments; Protein Binding; Protein Conformation; Virus Replication - drug effects; Monte Carlo method; Active site; Orthohepadnavirus; Modeling; Biological activity; Clevudine; Virus; Three dimensional model; Hepadnaviridae; Molecular model; Force field method; Antiviral; Hepatitis B virus; Mechanism of action; Pyrimidine nucleoside; Conformation; Polymerases
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(02)00747-3

The molecular dynamics simulation of HBV-polymerase·DNA· l-FMAU-TP complex demonstrated that l-FMAU-TP may not serve as a substrate for HBV polymerase because the appropriate binding of l-FMAU-TP to the active site of HBV polymerase may not take place without the unfavorable conformational adjustment, which prevents l-FMAU-TP from being incorporated into the growing viral DNA chain. The molecular dynamics simulation of HBV-polymerase·DNA· l-FMAU-TP complex is presented.