COARSE-GRAINED MODELING OF DNA PLECTONEME FORMATION IN THE PRESENCE OF BASE-PAIR MISMATCHES

Defects in double stranded DNA can arise from mismatched base pairs. In vivo, these must be rapidly repaired since they affect a variety of cell processes. Here we use molecular dynamics to study the effect of mismatched bps on DNA supercoiling. Magnetic tweezers-based studies of DNA supercoiling have shown that in DNA harboring a single mismatch, the plectoneme always localizes at the mismatch. These studies were conducted at relatively high salt concentrations (>0.5M). Theoretical studies have predicted that under physiological salt concentrations of ~0.2M, plectoneme localization becomes probabilistic. However, both approaches are currently limited to positively supercoiled DNA. We develop a simulation framework using the oxDNA model to study the effect of mismatches on both positively and negatively supercoiled DNA. We find that for a positively supercoiled DNA, the oxDNA framework can reproduce the experimentally observed plectoneme pinning at high force and high salt concentrations. Under physiological salt concentrations (0.2M), we find that the plectoneme localization at the mismatch becomes probabilistic. The utility of the simulation approach is highlighted by the ability to quantify the effect of mismatches on the motion of plectonemes along the DNA molecule.