title: Structural insights into the effect of isonucleosides on B-DNA duplexes using molecular-dynamics simulations.
abstract: Some structural insights into the conformations of the isonucleosides containing duplexes have been provided. Unrestrained molecular-dynamics simulations on 18-mer duplexes with isonucleosides incorporated at the 3'-end or in the center of one strand have been carried out with explicit solvent under periodic boundary conditions using the AMBER force field and the particle mesh Ewald method. The Watson-Crick hydrogen-bonding patterns of the duplexes studied remained intact throughout the simulation. For the modified duplexes, the changes observed in the inter-base pair parameters and backbone torsional angles were primarily localized at the isonucleoside-inserted area. All five structures studied remained in the B-form family. The decreased stacking abilities indicated by the large changes in inter-base pair parameters and the large changes in backbones made the modified duplexes show a minor thermal destabilization in comparison with native DNA. The MM_PBSA method for estimating binding free energies on two complementary strands was used. The results showed that the binding free energies of isonucleoside-incorporated DNA duplexes were lower than the native DNA duplex, which is in good agreement with experimental observations.
authors.affiliation: National Research Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100083, People's Republic of China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Jin
authors.forename: Suxin
authors.initials: S
authors.lastname: Zheng
authors.forename: Zhanli
authors.initials: Z
authors.lastname: Wang
authors.forename: Cheng
authors.initials: C
authors.lastname: Luo
authors.forename: Jianhua
authors.initials: J
authors.lastname: Shen
authors.forename: Hualiang
authors.initials: H
authors.lastname: Jiang
authors.forename: Liangren
authors.initials: L
authors.lastname: Zhang
authors.forename: Lihe
authors.initials: L
authors.lastname: Zhang
mesh_terms: D003198:Computer Simulation; D004247:DNA / Q000737:chemistry*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009705:Nucleosides / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D009705:Nucleosides; D004247:DNA