Molecular Dynamics Simulation of Supercoiled DNA with Mismatched Base Pair-Probing the Role of Structural Defect on Plectoneme Pinning

Mismatch repair (MMR) proteins correct mismatches in DNA. The exact mechanism by which MMR proteins recognize mismatch is still not well understood, but it is believed that the process involves introducing a sharp bend in the DNA and flipping out the mismatched base. Recent, single-molecule magnetic tweezers-based DNA supercoiling studies, conducted at salt concentrations of 0.5 M NaCl and higher, have shown that the mismatched base pair will always localizes at the end of the plectoneme loop and this may facilitate mismatch detection. Theoretical studies have found that the localization of mismatched base pair in the plectoneme end loop, at 0.2 M NaCl, becomes probabilistic. However, these studies were limited to positively supercoiled DNA. Here, we carry out molecular dynamics simulation to study supercoiling of DNA in presence of mismatched base pairs. We study both positively and negatively supercoiled DNA at salt concentration of 0.2 M NaCl using the oxDNA model. We simulate a DNA molecule with 0, 2, 4 and 6 consecutive G:T type mismatches. We find that the plectoneme localization at the mismatched base pair becomes probabilistic. We will present the details of the relation between the number of mismatched base pairs and the probability of plectoneme localization.