Mendieta-Moreno Jesús I, Trabada Daniel G, Mendieta Jesús, Lewis James P, Gómez-Puertas Paulino, Ortega José
Departamento de Física Teórica de la Materia Condensada and Condensed Matter Physics Center (IFIMAC), Universidad Autónoma de Madrid , ES-28049 Madrid, Spain.
Molecular Modelling Group, Center of Molecular Biology Severo Ochoa (CSIC-UAM) , ES-28049 Madrid, Spain.
J Phys Chem Lett. 2016 Nov 3;7(21):4391-4397. doi: 10.1021/acs.jpclett.6b02168. Epub 2016 Oct 25.
The absorption of ultraviolet radiation by DNA may result in harmful genetic lesions that affect DNA replication and transcription, ultimately causing mutations, cancer, and/or cell death. We analyze the most abundant photochemical reaction in DNA, the cyclobutane thymine dimer, using hybrid quantum mechanics/molecular mechanics (QM/MM) techniques and QM/MM nonadiabatic molecular dynamics. We find that, due to its double helix structure, DNA presents a free energy barrier between nonreactive and reactive conformations leading to the photolesion. Moreover, our nonadiabatic simulations show that most of the photoexcited reactive conformations return to standard B-DNA conformations after an ultrafast nonradiative decay to the ground state. This work highlights the importance of dynamical effects (free energy, excited-state dynamics) for the study of photochemical reactions in biological systems.
DNA对紫外线辐射的吸收可能会导致有害的基因损伤，影响DNA复制和转录，最终导致突变、癌症和/或细胞死亡。我们使用量子力学/分子力学（QM/MM）混合技术和QM/MM非绝热分子动力学，分析了DNA中最丰富的光化学反应——环丁烷胸腺嘧啶二聚体。我们发现，由于其双螺旋结构，DNA在非反应性和导致光损伤的反应性构象之间存在自由能垒。此外，我们的非绝热模拟表明，大多数光激发的反应性构象在超快非辐射衰变到基态后会回到标准的B-DNA构象。这项工作突出了动力学效应（自由能、激发态动力学）在生物系统光化学反应研究中的重要性。
