The base flipping of A-DNA—a molecular dynamic simulation study

Abstract

Due to different solvent conditions, double helix DNA exists in various conformations, such as B-DNA, A-DNA, C-DNA and Z-DNA. Recent studies have found that A-DNA is present in complexes with proteins, and has an important biological role in the context of cellular defense mechanisms under harsh conditions. In this study, the well-tempered meta-dynamics (WTM-eABF) were used to explore the free energy barriers for base ipping of the four natural bases, Adenine, Guanine, Cytosine, and Thymine in both A-form and B-form DNA duplex. The results show that the free energy barriers for base ipping was lower in A-DNA than that in B-DNA for all of the four natural bases. We analyzed the factors that may affect base ipping, such as π-π stacking, SASA, and conformational changes, and proved that conformational changes and π-π stacking are the most important factors affecting base ipping.