High hydrostatic pressure can have profound effects on the stability of biomacromolecules. The magnitude and direction (stabilizing or destabilizing) of this effect is defined by the volume changes in the system, ΔV. Positive volume changes will stabilize the starting native state, whereas negative volume changes will lead to the stabilization of the final unfolded state. For the DNA double helix, experimental data suggested that when the thermostability of dsDNA is below 50°C, increase in hydrostatic pressure will lead to destabilization; i.e., helix-to-coil transition has negative ΔV. In contrast, the dsDNA sequences with the thermostability above 50°C showed positive ΔV values and were stabilized by hydrostatic pressure. In order to get insight into this switch in the response of dsDNA to hydrostatic pressure as a function of temperature, first we further validated this trend using experimental measurements of ΔV for 10 different dsDNA sequences using pressure perturbation calorimetry. We also developed a computational protocol to calculate the expected volume changes of dsDNA unfolding, which was benchmarked against the experimental set of 50 ΔV values that included, in addition to our data, the values from the literature. Computation predicts well the experimental values of ΔV. Such agreement between computation and experiment lends credibility to the computation protocol and provides molecular level rational for the observed temperature dependence of ΔV that can be traced to the hydration. Difference in the ΔV value for A/T versus G/C basepairs is also discussed.

高静水压力会对生物大分子的稳定性产生深远的影响。该效应的大小和方向（稳定或不稳定）由系统中的体积变化 Δ V定义。正体积变化将稳定起始自然状态，而负体积变化将导致最终展开状态稳定。对于DNA双螺旋，实验数据表明，当双链DNA的热稳定性低于50℃时，静水压的增加会导致不稳定；即，螺旋到线圈的转变具有负ΔV 。相反，热稳定性高于 50°C 的 dsDNA 序列显示出正的ΔV值，并通过静水压稳定。为了深入了解 dsDNA 对静水压力的响应随温度变化的变化，首先，我们使用压力扰动量热法对 10 个不同 dsDNA 序列进行实验测量 Δ V ，进一步验证了这一趋势。我们还开发了一种计算协议来计算 dsDNA 展开的预期体积变化，该协议以 50 个 Δ V值的实验集为基准，除了我们的数据外，还包括文献中的值。计算很好地预测了 Δ V的实验值。计算和实验之间的这种一致性为计算协议提供了可信度，并为观察到的可追溯到水合的 Δ V温度依赖性提供了分子水平合理性。还讨论了 A/T 与 G/C 碱基对的 Δ V值的差异。