title: Stabilization of duplex DNA and RNA by dangling ends studied by free energy simulations.
abstract: Single unpaired nucleotides at the end of double-stranded nucleic acids, termed dangling ends, can contribute to duplex stability. Umbrella sampling free energy simulations of dangling cytosine and guanine nucleotides at the end of duplex and single stranded RNA and DNA molecules have been used to investigate the molecular origin of dangling end effects. In unrestraint simulations, the dangling end nucleotides stayed close to placements observed in experimental structures. Calculated free energy contributions associated with the presence of dangling nucleotides were in reasonable agreement with experiment predicting the general trend of a more stabilizing effect of purine vs. pyrimidine dangling ends. In addition, the calculations indicate a more significant stabilizing effect of dangling ends at the 5'-end vs. 3'-end in case of DNA and the opposite trend in case of RNA. Both electrostatic and van der Waals interactions contribute to the duplex stabilizing effect of dangling end nucleotides. The free energy simulation scheme could also be used to design dangling end nucleotides that result in enhanced duplex stabilization.
authors: Physik-Department T38, Technische Universität München, James-Franck-Str. 1,, 85747, Garching, Germany.
authors: Mahmut
authors: M
authors: Kara
authors: Martin
authors: M
authors: Zacharias
mesh_terms: D003198:Computer Simulation; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D009692:Nucleic Acid Heteroduplexes / Q000737:chemistry*; D009711:Nucleotides / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D009692:Nucleic Acid Heteroduplexes; D009711:Nucleotides
keywords: end effects on nucleic acids; molecular dynamics simulation; nucleic acid duplex formation; nucleic acid hybridization; nucleic acid stability