Simulation Study Of The Micromechanical Stability Of DNA Hairpin Structure

Defect structures such as base mismatches and base deletions often occur in certain life processes related to DNA,leading to various serious consequences such as gene mutations,and their identification is very difficult,becoming the focus of current single-molecule research.The paper is based on the extended ox-DNA model to detect the influence of base mismatches on the stability of DNA hairpin structures and to validate the existence of intermediate states.The DNA hairpin structure used in the simulation study has a stem length of 12-20bp(base-pair)and a loop of 4T.A G-T base mismatch is introduced in the stem,and the position of the defect relative to the loop is gradually adjusted to systematically study the dynamic and thermodynamic properties of the DNA hairpin structure transition.The influence of base mismatches on the stability of DNA hairpin structures was explored by simulating the application of constant force(hopping)and force-ramping with a certain rate at both ends of the DNA hairpin.The intersection point of the opening and closing kinetic rates related to the force was defined as the critical force.By analyzing the data,it was found that the introduction of base mismatches reduced the critical force of DNA hairpin.When the force gradually increased to a higher level at a constant loading rate,the sudden jump on the force-extension curve corresponded to the first breaking force.By analyzing the data,it was found that the introduction of base mismatches reduced the first breaking force of DNA hairpin.Based on the previous work,base mismatches were introduced at different positions in the stem of DNA hairpin,and by comparing the size of the critical force,it was found that the critical force was the smallest when the base mismatch was in the middle position of the stem of DNA hairpin.Further analysis of the opening probability of DNA hairpin also yielded consistent results.These results indicate that base mismatches reduce the stability of the DNA hairpin structure,and that the stability is maximally reduced when the base mismatch is in the middle position of the stem of DNA hairpin.The intermediate state caused by base mismatches was explored.By applying a constant force at both ends of the DNA hairpin and observing the third peak in the extension probability distribution and the third local potential well in the free energy surface,the characteristics of the intermediate state caused by base mismatches and its dependence on the location of the base mismatch in the stem can be obtained.Furthermore,this dependence was generalized into a phase diagram about the proportion of base mismatch positions,and the range of base mismatch positions with intermediate states was obtained.In the phase diagram,the three segments on the diagonal correspond to the proportion position range of base mismatches: [0,0.55),[0.55,0.85)and [0.85,1].In the range of [0.55,0.85),the DNA hairpin exists in three states: closed,intermediate,and open,while in the other two proportion ranges,only closed and open states exist.