College of Physics and Electronics, Shandong Normal University, Jinan, 250014, China.
College of Chemistry, Shandong Normal University, Jinan, 250014, China.
Sci Rep. 2017 Aug 10;7(1):7798. doi: 10.1038/s41598-017-08219-z.
Combining multi-level quantum mechanics theories and molecular mechanics with an explicit water model, we investigated the ring opening process of guanine damage by hydroxyl radical in aqueous solution. The detailed, atomic-level ring-opening mechanism along the reaction pathway was revealed in aqueous solution at the CCSD(T)/MM levels of theory. The potentials of mean force in aqueous solution were calculated at both the DFT/MM and CCSD(T)/MM levels of the theory. Our study found that the aqueous solution has a significant effect on this reaction in solution. In particular, by comparing the geometries of the stationary points between in gas phase and in aqueous solution, we found that the aqueous solution has a tremendous impact on the torsion angles much more than on the bond lengths and bending angles. Our calculated free-energy barrier height 31.6 kcal/mol at the CCSD(T)/MM level of theory agrees well with the one obtained based on gas-phase reaction profile and free energies of solvation. In addition, the reaction path in gas phase was also mapped using multi-level quantum mechanics theories, which shows a reaction barrier at 19.2 kcal/mol at the CCSD(T) level of theory, agreeing very well with a recent ab initio calculation result at 20.8 kcal/mol.
我们结合多层次量子力学理论和分子力学，采用显式水分子模型，研究了水溶液中羟基自由基对鸟嘌呤损伤的开环过程。在 CCSD(T)/MM 理论水平上，揭示了水溶液中沿反应途径的详细原子级开环机制。在 DFT/MM 和 CCSD(T)/MM 理论水平上计算了水溶液中的平均力势。我们的研究发现，水溶液对该反应在溶液中的影响显著。特别是，通过比较气相和水溶液中稳定点的几何形状，我们发现水溶液对扭转角的影响远大于对键长和弯曲角的影响。我们在 CCSD(T)/MM 理论水平上计算得到的自由能势垒高度为 31.6 kcal/mol，与基于气相反应轮廓和溶剂化自由能得到的结果非常吻合。此外，还使用多层次量子力学理论映射了气相中的反应路径，该路径在 CCSD(T)理论水平上显示出 19.2 kcal/mol 的反应势垒，与最近的 20.8 kcal/mol 的从头计算结果非常吻合。
