(713a) Structural and Thermodynamic Characteristics of Mutated DNA Containing Mismatched Base Pair Using Steered Molecular Dynamic Simulation

DNA is a key molecule of life since it is the repository of genetic information in each living cell. Despite the fact that its integrity and stability are essential to life, DNA is not inert; rather, it is a chemical entity subject to assault from the environment, and any resulting damage will lead to mutation and possibly disease. During the replication, while most DNA replicates with fairly high fidelity, mistakes occur during this copying process with polymerase enzymes inserting the wrong nucleotide and trigger major biological consequences.  In this study, using molecular dynamics (MD) simulation, we present detailed information on structural changes of mutated double stranded DNA (dsDNA) that contains a mismatched base pair, at resolution not yet accessible to current experimental techniques. Especially focused on the force-induced mechanical deformation, nine-base-pair-long mutated dsDNA and that of normal dsDNA are extended by pulling two 5’ ends of each strand at a constant rate using Steered MD simulation. During the extension, the structural change is monitored in terms of the hydrogen bonding geometry in each base pair, end-to-end distance, the change in length of backbone of helical structure, and potential mean force. For the comparison of mutated dsDNA with normal dsDNA on their structural characteristic, the energy and force between two strands of both mutated dsDNA and normal DNA during the deformation are analyzed to see how the interaction changes, mostly due to the hydrogen bonding contribution.