Characterization of the effect of functional groups substitution at the 2-position of adenine on the stability of a duplex dodecamer d(CGCGAATTCGCG)2 by molecular mechanics and free energy perturbation method

Abstract

The dynamical structure and stability of duplex DNA is closely related to biological phenomena such as transcription, replication and regulation of gene expression. The modification of bases in DNA is known to have an important influence on the biological function of DNA. Modified bases cause a change in the structure and stability of DNA and, as a result, the interaction of enzymes and regulatory proteins with DNA is modified. There are several reports [1–6] in which the structure change of DNA by base modification is theoretically treated using molecular modeling, molecular mechanics and quantum chemistry, but few studies have adopted a dynamical approach such as molecular dynamics and free energy calculation. Thus, we tried such a dynamical approach to understand the effect of base modification on the stability of the DNA duplex.