Materials Science and Engineering Division, National Institute of Standards and Technology, Gaithersburg, MD 20899, USA.
Soft Matter. 2017 Nov 15;13(44):8309-8330. doi: 10.1039/c7sm01220a.
Enthalpy-entropy compensation (EEC) is observed in diverse molecular binding processes of importance to living systems and manufacturing applications, but this widely occurring phenomenon is not sufficiently understood from a molecular physics standpoint. To gain insight into this fundamental problem, we focus on the melting of double-stranded DNA (dsDNA) since measurements exhibiting EEC are extensive for nucleic acid complexes and existing coarse-grained models of DNA allow us to explore the influence of changes in molecular parameters on the energetic parameters by using molecular dynamics simulations. Previous experimental and computational studies have indicated a correlation between EEC and changes in molecular rigidity in certain binding-unbinding processes, and, correspondingly, we estimate measures of DNA molecular rigidity under a wide range of conditions, along with resultant changes in the enthalpy and entropy of binding. In particular, we consider variations in dsDNA rigidity that arise from changes of intrinsic molecular rigidity such as varying the associative interaction strength between the DNA bases, the length of the DNA chains, and the bending stiffness of the individual DNA chains. We also consider extrinsic changes of molecular rigidity arising from the addition of polymer additives and geometrical confinement of DNA between parallel plates. All our computations confirm EEC and indicate that this phenomenon is indeed highly correlated with changes in molecular rigidity. However, two distinct patterns relating to how DNA rigidity influences the entropy of association emerge from our analysis. Increasing the intrinsic DNA rigidity increases the entropy of binding, but increases in molecular rigidity from external constraints decreases the entropy of binding. EEC arises in numerous synthetic and biological binding processes and we suggest that changes in molecular rigidity might provide a common origin of this ubiquitous phenomenon in the mutual binding and unbinding of complex molecules.
焓熵补偿（EEC）在对生命系统和制造应用很重要的各种分子结合过程中都有观察到，但从分子物理的角度来看，这种广泛存在的现象并没有得到充分的理解。为了深入了解这个基本问题，我们专注于双链 DNA（dsDNA）的熔化，因为对于核酸复合物来说，表现出 EEC 的测量结果非常广泛，并且现有的粗粒化 DNA 模型允许我们通过分子动力学模拟来探索分子参数变化对能量参数的影响。以前的实验和计算研究表明，EEC 与某些结合-解吸过程中分子刚性的变化之间存在相关性，相应地，我们在广泛的条件下估计 DNA 分子刚性的度量，以及结合焓和熵的相应变化。特别是，我们考虑了 dsDNA 刚性的变化，这些变化源于内在分子刚性的变化，例如改变 DNA 碱基之间的缔合相互作用强度、DNA 链的长度以及单个 DNA 链的弯曲刚度。我们还考虑了由聚合物添加剂的添加和 DNA 在平行板之间的几何约束引起的分子刚性的外在变化。我们所有的计算都证实了 EEC，并表明这种现象确实与分子刚性的变化高度相关。然而，从我们的分析中出现了两种与 DNA 刚性如何影响关联熵相关的不同模式。增加内在 DNA 刚性会增加结合熵，但来自外部约束的分子刚性增加会降低结合熵。EEC 出现在许多合成和生物结合过程中，我们认为分子刚性的变化可能为复杂分子相互结合和解离的这种普遍现象提供了一个共同的起源。
