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

Due to different solvent conditions, double helix DNA exists in various conformations, such as B-DNA, A-DNA, C-DNA, and Z-DNA. 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 flipping 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 flipping were lower in A-DNA than that in B-DNA for all of the four natural bases. We analyzed the factors that may affect base flipping, such as π-π stacking, SASA, H-bonding, and conformational changes, and concluded that conformational changes and π-π stacking are the most important factors affecting base flipping.