Base flipping in DNA: Pathways and energetics studied with molecular dynamic simulations

Carrying out chemistry on the bases of DNA, necessary for biological processes such as methylation or repair, requires flipping the base into an accessible position. In this work, molecular dynamics simulations are used to generate a free energy profile for flipping a cytosine base out of its helical stack in double-stranded DNA. The results shed light on the mechanics of this process by comparing routes for base flipping via the minor and major grooves.