Studying the DNA hybridization equilibrium via brute force molecular dynamics (MD) or commonly used advanced sampling approaches is notoriously difficult at the atomistic length scale. However, besides providing more realistic modeling of this microscopic phenomenon, the atomistic resolution is a necessity for some fundamental research questions, such as the ones related to DNA's chirality. Here, we describe an order parameter-based advanced sampling technique to calculate the free energy surface of hybridization and estimate the melting temperature of DNA oligomers at the atomistic resolution, using a native topology-based order parameter. We show that the melting temperatures estimated from our atomistic simulations follow an order consistent with the predictions from melting experiments and those from the nearest neighbor model, for a range of DNA sequences of different GC content. Moreover, free energy surfaces and melting temperatures are calculated to be identical for D- and L-enantiomers of Drew-Dickerson dodecamer.

中文翻译：

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基于原子模拟的DNA杂交热力学

在原子长度尺度上，通过蛮力分子动力学（MD）或常用的高级采样方法研究DNA杂交平衡是非常困难的。但是，除了提供对这种微观现象的更真实的建模之外，原子分辨率对于某些基础研究问题（例如与DNA手性有关的问题）也是必需的。在这里，我们描述了一种基于顺序参数的高级采样技术，可使用基于本地拓扑的顺序参数来计算杂交的自由能表面并以原子分辨率估算DNA低聚物的解链温度。我们证明，根据原子模拟得出的熔化温度遵循的顺序与熔化实验和最近邻模型的预测一致，用于一系列具有不同GC含量的DNA序列。此外，对于Drew-Dickerson dodecamer的D和L对映体，自由能表面和熔化温度经计算为相同。