Computational investigation of locked nucleic acid (LNA) nucleotides in the active sites of DNA polymerases by molecular docking simulations

PLoS One. 2014 Jul 18;9(7):e102126. doi: 10.1371/journal.pone.0102126. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalytic Domain*
  • DNA-Directed DNA Polymerase / chemistry*
  • DNA-Directed DNA Polymerase / metabolism*
  • Molecular Docking Simulation*
  • Nucleic Acid Conformation
  • Oligonucleotides / chemistry
  • Oligonucleotides / metabolism*
  • Polyphosphates / chemistry

Substances

  • Oligonucleotides
  • Polyphosphates
  • locked nucleic acid
  • DNA-Directed DNA Polymerase
  • triphosphoric acid

Grants and funding

This work is supported by the Nucleic Acid Center, University of Southern Denmark. RNV also acknowledges the Fellowship from the University of Queensland. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.