Structural Insights into the Effect of Isonucleosides on B-DNA Duplexes Using Molecular-dynamics Simulations

Overview

Journal J Mol Model

Publisher Springer

Specialty Molecular Biology

Date 2006 Feb 2

PMID 16450112

Authors

Hongwei Jin

Suxin Zheng

Zhanli Wang

Cheng Luo

Jianhua Shen

Hualiang Jiang

Liangren Zhang

Lihe Zhang

Affiliations

Soon will be listed here.

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.

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