Title: DNA Base Pair Mismatches Induce Structural Changes and Alter the Free Energy Landscape of Base Flip,
Abstract: Double-stranded DNA may contain mismatched base pairs beyond the Watson-Crick
pairs guanine-cytosine and adenine-thymine. Such mismatches bear adverse
consequences for human health. We utilize molecular dynamics and metadynamics
computer simulations to study the equilibrium structure and dynamics for both
matched and mismatched base pairs. We discover significant differences between
matched and mismatched pairs in structure, hydrogen bonding, and base flip work
profiles. Mismatched pairs shift further in the plane normal to the DNA strand
and are more likely to exhibit non-canonical structures, including the e-motif.
We discuss potential implications on mismatch repair enzymes' detection of DNA
mismatches.