title: Applications of quantum mechanical/molecular mechanical methods to the chemical insertion step of DNA and RNA polymerization.
abstract: We review theoretical attempts to model the chemical insertion reactions of nucleoside triphosphates catalyzed by the nucleic acid polymerases using combined quantum mechanical/molecular mechanical methodology. Due to an existing excellent database of high-resolution X-ray crystal structures, the DNA polymerase β system serves as a useful template for discussion and comparison. The convergence of structures of high-quality complexes and continued developments of theoretical techniques suggest a bright future for understanding the global features of nucleic acid polymerization.
authors.affiliation: Laboratory of Structural Biology, National Institution of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. Electronic address: pereral2@niehs.nih.gov.
authors.forename: Lalith
authors.initials: L
authors.lastname: Perera
authors.affiliation: Laboratory of Structural Biology, National Institution of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Beard
authors.affiliation: Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Lee G
authors.initials: LG
authors.lastname: Pedersen
authors.affiliation: Laboratory of Structural Biology, National Institution of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Wilson
mesh_terms: D001665:Binding Sites; D055162:Biocatalysis; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry*; D019951:DNA Polymerase beta / Q000737:chemistry*; D012321:DNA-Directed RNA Polymerases / Q000737:chemistry*; D006801:Humans; D056004:Molecular Dynamics Simulation; D058105:Polymerization; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011789:Quantum Theory; D012313:RNA / Q000737:chemistry*
chemical_list: D012313:RNA; D004247:DNA; D012321:DNA-Directed RNA Polymerases; D019951:DNA Polymerase beta
keywords: DNA polymerase; DNA repair; Enzyme catalysis; Nucleotide insertion; Polymerase β; Proton transfer; QM/MM; RNA polymerase; Reaction paths