Structural Insights into the Effect of Isonucleosides on B-DNA Duplexes using Molecular Dynamics Simulations
Some structural insights into the conformations of the isonucleosides containing duplexes have been provided. Unrestrained molecular dynamics simulations on 18mer 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 AMBER force field and particle mesh Ewald method. The Watson-Crick hydrogen-bonding patterns of the studied duplexes 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 isonucleosides inserted area. All five studied structures 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 utilized. The results showed that the binding free energies of isonucleosides incorporated DNA duplexes were lower the native DNA duplex, which were in good agreement with experimental observations. The software used in this work are Insight Ⅱ, Amber 7.0 and Gaussian 98.
MD simulations·Isonucleoside·Backbone·Helix parameter·Thermal stability
Hongwei Jin Suxin Zheng Zhanli Wang Cheng Luo Jianhua Shen Hualiang Jiang Liangren Zhang Lihe Zhang
National Research Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Pek Shanghai Institute of Materia Medica, Chinese Academy of Sciences,Shanghai 201203, China
国际会议
杭州
英文
1339-1359
2007-04-01（万方平台首次上网日期，不代表论文的发表时间）