Recombinant Triplex formed by PNA-TFO: A Molecular Dynamics Simulation Study

Abstract

Building of high affinity triplex-forming oligonucleotides(TFOs) enhances its therapeutical application. Peptide nucleic acid(PNA), a modified DNA oligomer with neutral backbone enhances the affinity of TFO. MD simulation method is very helpful to study the stability, affinity and behavior of complex at nanosecond scale. Therefore a 15-mer PNA-TFO is used here to model DNA:DNA:PNA triplex in mixed purine/pyrimidine sequence. DNA:DNA:DNA triplex, DNA:DNA duplex and DNA:PNA duplex were also modeled for comparison. 100ns of MD run on all four complexes in solution at neutral pH. The triplex conformation stabilized with Recombinant type(R-type) of Hydrogen bonding during simulation. The rmsd of DNA:DNA:PNA triplex and DNA:DNA:DNA triplex converges after 45 ns of dynamics and the binding affinity of PNA-TFO found greater than DNA-TFO. Together with non-toxicity of PNA oligomer, stable triplex formation with R-type of hydrogen bonding pattern and high binding affinity in mixed sequence promotes the study regarding Recombinant triplex with PNA-TFO.