title: Conformational studies of chiral D-Lys-PNA and achiral PNA system in binding with DNA or RNA through a molecular dynamics approach.
abstract: The growing interest in peptide nucleic acid (PNA) oligomers has led to the development of a very wide variety of PNA derivatives. Among others, the introduction of charged chiral groups on a PNA oligomer has proven effective in improving DNA binding ability, complexation direction and cellular uptake. In particular, the introduction of three adjacent chiral monomers based on D-Lys in the middle of the PNA sequence (D-Lys-PNA) has produced noteworthy results in modulating the directionality of the binding with the DNA complementary strand and in mismatch detection. Here, through a molecular dynamics approach, a comparative study has been carried out to investigate the structural properties that drive the interaction of the chiral D-Lys-PNA and the corresponding achiral PNA system with DNA as well as RNA complementary strands, starting from the crystal structure of D-Lys-PNA in complex with DNA. The results obtained complement experimental data and indicate that the binding with the RNA molecule, compared to DNA, is differently affected by the addition of three D-Lys groups on the PNA backbone, suggesting that this modification could be taken into account for the development of new PNA-based molecules able to discriminate between DNA and RNA.
authors.affiliation: National Research Council, Institute of Biostructures and Bioimaging, 80134 Naples, Italy.
authors.forename: Ida
authors.initials: I
authors.lastname: Autiero
authors.affiliation: National Research Council, Institute of Crystallography, 70126 Bari, Italy. Electronic address: msaviano@unina.it.
authors.forename: Michele
authors.initials: M
authors.lastname: Saviano
authors.affiliation: National Research Council, Institute of Biostructures and Bioimaging, 80134 Naples, Italy. Electronic address: emma.langella@cnr.it.
authors.forename: Emma
authors.initials: E
authors.lastname: Langella
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry*; D007700:Kinetics; D008239:Lysine / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D020135:Peptide Nucleic Acids / Q000737:chemistry*; D011485:Protein Binding; D012313:RNA / Q000737:chemistry*; D055672:Static Electricity; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D020135:Peptide Nucleic Acids; D012313:RNA; D004247:DNA; D008239:Lysine
keywords: Conformation; DNA; Molecular dynamics; Peptide nucleic acid; RNA