A Deep Dive into DNA Base Pairing Interactions Under Water
A Deep Dive into DNA Base Pairing Interactions Under Water
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DOI：
10.1021/acs.jpcb.0c03069
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发表时间：
2020-07-09
影响因子：
3.3
通讯作者：
Mak, Chi H.
中科院分区：
文献类型：
--
作者：
Li, Rongpeng;Mak, Chi H.
碱基配对在DNA功能和复制保真度中起着关键作用。但是，虽然沃森-克里克匹配碱基之间的互补性通常被认为是由于G竖杆C对与A竖杆T对中氢键数量的不同而产生的，但这些相互作用的能量学被水溶液严重地重整了。利用大规模的蒙特卡罗模拟，我们提取了典型和一些非典型和堆叠碱基对的溶剂对自由能的贡献。对于所有这些，溶剂对碱对自由能的贡献都是不稳定的。虽然G b| C对中的直接氢键相互作用比A纵杆T强得多，但溶剂对G纵杆C产生的热力学阻力也比A纵杆T强得多，两者之间产生的自由能差仅类似于1千卡/摩尔。我们描绘了碱基附近溶剂中水分子的密度，并观察到一种“冻结”行为，在这种情况下，水被吸收到碱基之间的空隙中，以补偿它们之间未满足的氢键。与沃森-克里克供体/受体原子相关联的极少数水分子是导致溶剂对碱基配对的大部分热力学阻力的原因。这些近场水的存在或缺失可以用来提高DNA复制过程中的保真度。
Base pairing plays a pivotal role in DNA functions and replication fidelity. But while the complementarity between Watson-Crick matched bases is generally believed to arise from the different number of hydrogen bonds in G vertical bar C pairs versus A vertical bar T, the energetics of these interactions are heavily renormalized by the aqueous solvent. Employing large-scale Monte Carlo simulations, we have extracted the solvent contribution to the free energy for canonical and some noncanonical and stacked base pairs. For all of them, the solvent's contribution to the base pairing free energy is exclusively destabilizing. While the direct hydrogen bonding interactions in the G|C pair is much stronger than A vertical bar T, the thermodynamic resistance produced by the solvent also pushes back much stronger against G vertical bar C compared to A vertical bar T, generating an only similar to 1 kcal/mol free energy difference between them. We have profiled the density of water molecules in the solvent adjacent to the bases and observed a "freezing" behavior where waters are recruited into the gap between the bases to compensate for the unsatisfied hydrogen bonds between them. A very small number of water molecules that are associated with the Watson-Crick donor/acceptor atoms turn out to be responsible for the majority of the solvent's thermodynamic resistance to base pairing. The absence or presence of these near-field waters can be used to enhance fidelity during DNA replication.