title: A computational chemistry perspective on the current status and future direction of hepatitis B antiviral drug discovery.
abstract: Computational chemical biology, applied to research on hepatitis B virus (HBV), has two major branches: bioinformatics (statistical models) and first-principle methods (molecular physics). While bioinformatics focuses on statistical tools and biological databases, molecular physics uses mathematics and chemical theory to study the interactions of biomolecules. Three computational techniques most commonly used in HBV research are homology modeling, molecular docking, and molecular dynamics. Homology modeling is a computational simulation to predict protein structure and has been used to construct conformers of the viral polymerase (reverse transcriptase domain and RNase H domain) and the HBV X protein. Molecular docking is used to predict the most likely orientation of a ligand when it is bound to a protein, as well as determining an energy score of the docked conformation. Molecular dynamics is a simulation that analyzes biomolecule motions and determines conformation and stability patterns. All of these modeling techniques have aided in the understanding of resistance mutations on HBV non-nucleos(t)ide reverse-transcriptase inhibitor binding. Finally, bioinformatics can be used to study the DNA and RNA protein sequences of viruses to both analyze drug resistance and to genotype the viral genomes. Overall, with these techniques, and others, computational chemical biology is becoming more and more necessary in hepatitis B research. This article forms part of a symposium in Antiviral Research on "An unfinished story: from the discovery of the Australia antigen to the development of new curative therapies for hepatitis B."
authors.affiliation: Department of Chemistry, Baruch S. Blumberg Institute, Doylestown, PA 18902, USA.
authors.forename: Dante
authors.initials: D
authors.lastname: Morgnanesi
authors.affiliation: Department of Chemistry, Baruch S. Blumberg Institute, Doylestown, PA 18902, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Heinrichs
authors.affiliation: Department of Chemistry, Baruch S. Blumberg Institute, Doylestown, PA 18902, USA.
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Mele
authors.affiliation: Department of Chemistry, Baruch S. Blumberg Institute, Doylestown, PA 18902, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: Wilkinson
authors.affiliation: Department of Chemistry, Baruch S. Blumberg Institute, Doylestown, PA 18902, USA.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Chemistry, Baruch S. Blumberg Institute, Doylestown, PA 18902, USA. Electronic address: john.kulp@bblumberg.org.
authors.forename: John L
authors.initials: JL
authors.lastname: Kulp
mesh_terms: D000998:Antiviral Agents / Q000302:isolation & purification* / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D019295:Computational Biology; D055808:Drug Discovery / Q000379:methods* / Q000639:trends; D024882:Drug Resistance, Viral; D005838:Genotype; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation
chemical_list: D000998:Antiviral Agents
keywords: Bioinformatics; Computational chemical biology; Hepatitis B virus; Homology modeling; Molecular docking; Molecular dynamics