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DNA是大部分生物包括病毒的基因载体。DNA双螺旋链通过A=T和G≡C两种碱基对编码实现对遗传信息的存储。碱基对中的相互作用对DNA双螺旋链的稳定性起到重要作用,直接关系到基因的复制和转录。当前研究中,我们构建了四组不同结构的DNA双螺旋链,进行了总共4.3μs的分子动力学模拟。通过伞形取样技术计算了DNA双螺旋链中碱基对分离的自由能曲线,并从分子尺度细节和相互作用能对自由能曲线进行解析。在碱基对G≡C的自由能曲线(PMF-PGC)上观察到三个峰,通过监测氢键数目的变化发现分别对应于G≡C三个氢键的断裂;而在A=T的自由能曲线(PMF-PAT)上只出现一个峰,说明A=T的两个氢键在分离过程中几乎同时断裂。PMF-PGC的总能垒比PMF-PAT高,主要是因为G≡C比A=T多一个氢键,更稳定。两条曲线的后段自由能仍然升高,而此时碱基对的氢键已断裂,这是DNA链骨架刚性所导致。我们还研究了碱基对稳定性受相邻碱基对的影响,发现邻近G≡C碱基对会增强A=T的稳定性,C≡G会削弱A=T的稳定性,T=A对A=T的影响较小。
DNA is the genetic vector for most organisms, including viruses. DNA double helix chain through A = T and G≡C two base pairs of coding to achieve the storage of genetic information. The interaction of base pairs plays an important role in the stability of DNA double helix, which is directly related to gene duplication and transcription. In the current study, we constructed four sets of DNA double helix strands of different structures and performed a total of 4.3 μs molecular dynamics simulations. The free energy curves of base pairs in DNA double helix were calculated by umbrella sampling technique, and the free energy curves were analyzed from the details of molecular scale and interactions. Three peaks were observed on the free energy curve (PMF-PGC) of the base pair G≡C, and the breaks corresponding to the three hydrogen bonds of G≡C were found by monitoring the change of the number of hydrogen bonds. In the case of A = T Only one peak appears on the free energy curve (PMF-PAT), indicating that the two hydrogen bonds of A = T break almost simultaneously at the same time. The total energy barrier of PMF-PGC is higher than that of PMF-PAT, mainly because G≡C has more hydrogen bonds than A = T and is more stable. The free energy of the posterior segment of both curves is still elevated, while the hydrogen bonds of the base pairs have broken, which is caused by the rigidity of the DNA chain. We also investigated the stability of base pairs affected by adjacent base pairs and found that adjacent G≡C base pairs enhance A = T stability, C≡G weakens A = T stability, T = A A = T less affected.