title: Computational investigation of locked nucleic acid (LNA) nucleotides in the active sites of DNA polymerases by molecular docking simulations.
abstract: Aptamers constitute a potential class of therapeutic molecules typically selected from a large pool of oligonucleotides against a specific target. With a scope of developing unique shorter aptamers with very high biostability and affinity, locked nucleic acid (LNA) nucleotides have been investigated as a substrate for various polymerases. Various reports showed that some thermophilic B-family DNA polymerases, particularly KOD and Phusion DNA polymerases, accepted LNA-nucleoside 5'-triphosphates as substrates. In this study, we investigated the docking of LNA nucleotides in the active sites of RB69 and KOD DNA polymerases by molecular docking simulations. The study revealed that the incoming LNA-TTP is bound in the active site of the RB69 and KOD DNA polymerases in a manner similar to that seen in the case of dTTP, and with LNA structure, there is no other option than the locked C3'-endo conformation which in fact helps better orienting within the active site.
authors.affiliation: Nucleic Acid Center and Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense M, Denmark.
authors.forename: Vasanthanathan
authors.initials: V
authors.lastname: Poongavanam
authors.affiliation: Institute of Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Praveen K
authors.initials: PK
authors.lastname: Madala
authors.affiliation: Nucleic Acid Center and Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense M, Denmark.
authors.forename: Torben
authors.initials: T
authors.lastname: Højland
authors.affiliation: Nucleic Acid Center and Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense M, Denmark; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Rakesh N
authors.initials: RN
authors.lastname: Veedu
mesh_terms: D020134:Catalytic Domain; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry* / Q000378:metabolism*; D062105:Molecular Docking Simulation; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry / Q000378:metabolism*; D011122:Polyphosphates / Q000737:chemistry
chemical_list: D009841:Oligonucleotides; D011122:Polyphosphates; C477371:locked nucleic acid; D004259:DNA-Directed DNA Polymerase; C005692:triphosphoric acid