The recent discovery that Hoogsteen (HG) base pairs are widespread in DNA across diverse sequences and positional contexts could have important implications for understanding DNA replication and DNA–protein recognition. While evidence is emerging that the Hoogsteen conformation could be a thermodynamically accessible conformation of the DNA duplex and provide a means to expand its functionality, relatively little is known about the molecular mechanism underlying the Watson–Crick (WC) to HG transition. In this Perspective, we describe pathways and kinetics for this transition at an atomic level of detail, using the energy landscape perspective. We show that competition between the duplex conformations results in a double funnel landscape, which explains some recent experimental observations. The interconversion pathways feature a number of intermediates, with a variable number of WC and HG base pairs. The relatively slow kinetics, with possible deviations from two-state behavior, suggest that this conformational switch is likely to be a challenging target for both simulation and experiment.

中文翻译：

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沃森-克里克和Hoogsteen碱基配对在DNA中转换的能量态势和途径

最近发现Hoogsteen（HG）碱基对在DNA中广泛分布于不同的序列和位置环境中，这可能对理解DNA复制和DNA-蛋白质识别具有重要意义。尽管有证据表明Hoogsteen构象可能是DNA双链体的热力学可及构象，并提供了扩展其功能的手段，但对Watson-Crick（WC）转变为HG的分子机制知之甚少。在此“透视图”中，我们使用“能源格局”透视图以原子的详细程度描述了此过渡的途径和动力学。我们表明，双链体构象之间的竞争导致了双重漏斗态势，这解释了一些最近的实验观察结果。相互转化途径具有许多中间体，其中WC和HG碱基对的数目可变。相对较慢的动力学，可能偏离两种状态的行为，表明这种构象转换可能是模拟和实验的挑战性目标。