DNA Base Pair Mismatches Induce Structural Changes and Alter the Free Energy Landscape of Base Flip

TL;DR

This study uses molecular simulations to reveal how DNA mismatches cause structural changes and affect the energy landscape of base flipping, which may influence mismatch repair mechanisms.

Contribution

The paper provides detailed insights into the structural and energetic differences between matched and mismatched DNA base pairs through advanced simulation techniques.

Findings

Mismatched pairs show greater displacement and non-canonical structures.

Significant differences in hydrogen bonding and base flip work profiles.

Potential impact on mismatch repair enzyme recognition.

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.