![]() PNA is a synthetic nucleic acid analogue whose backbone contains N-(2-aminoethyl)-glycine units instead of sugar-phosphate units, 4 while keeping natural bases as side chains ( Figure 1). Another nucleic acid mimic, termed peptide nucleic acid (PNA), that we focus on in this study, has the entire sugar-phosphate backbone redesigned. 3 In the latter, the ribose ring is locked by a methylene bridge connecting the 2’-0 and 4’-C atoms. The modifications in the sugar ring include 2’O-methyl-RNA and locked nucleic acid (LNA). Common procedures are to replace one of the non-bridging oxygen atoms in the phosphate group with a sulphur (phosphorothioates), a methyl group (methylphosphonates) or a dimethylamine group (Morpholinos 2). Therefore, many modified oligonucleotides have been synthesized in an effort to make them both biostable and more specific for their target sequence. However, natural oligonucleotides are recognized by nucleases and, as a consequence, they are degraded. Therefore, the use of sequence-specific hybridization of short oligonucleotides to natural DNA or RNA targets has been a matter of extensive research. 1 Oligonucleotides that specifically recognize double-stranded DNA or messenger RNA modulate key biological processes of either transcription or translation. Short oligonucleotides that hybridize with a complementary fragment of DNA or RNA have been used in vitro and in vivo to regulate gene expression in diagnostic, therapeutic, and molecular biology applications. The concept of RNA or DNA silencing is widespread in nature. The atomistic details of unfolding of PNA duplexes suggest that all PNA-PNA bases melt concomitantly, whereas the RNA-RNA and PNA-RNA are destabilized from the termini toward the central part of the duplexes. The PNA-PNA duplex also displays the highest activation energy for melting. The simulations show a two-state melting transition and reproduce the thermal stability from melting experiments, with PNA-PNA being the most and RNA-RNA the least stable. ![]() We investigated thermal stabilities of short PNA-PNA, PNA-RNA and RNA-RNA duplexes using UV-monitored thermal denaturation experiments and MD simulations at ambient and elevated temperatures. In this work we provide the first application of this force field to biologically-relevant PNA sequences and their complexes with RNA. We have recently developed force field parameters for molecular dynamics (MD) simulations of PNA and PNA-involving duplexes with natural nucleic acids. In addition, PNA is biostable and thus used in many antisense and antigene applications to block functional RNA or DNA via sequence-specific interactions. PNA-nucleic acid complexes are more thermally stable than the corresponding complexes of natural nucleic acids. Peptide nucleic acid (PNA) is a neutral nucleic acid analogue that base pairs with itself and natural nucleic acids. ![]()
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