Entropy–enthalpy compensation is observed in many reactions, particularly for polymeric biomolecules that often involve large changes in entropy and enthalpy. The imperfect cancelation of entropy and enthalpy dictates many biophysical characteristics, such as protein thermodynamic stability and the free energy barrier for protein folding. In this study, we examine how tethering a conjugate to a protein may affect the thermodynamic stability of the protein. We found that a conjugate mostly affects the unfolded state by eliminating formation of some residual interactions. Consequently, both the enthalpy and the entropy of the unfolded state are affected. We suggest that, because this effect is not localized, the gain in conformational flexibility (i.e., increased entropy) is larger than the loss of some residual interaction (i.e., increased enthalpy). Therefore, the unfolded state of the conjugated protein has a lower free energy than that of the free protein, resulting in thermodynamic destabilization.

熵-焓补偿在许多反应中都可以观察到，特别是对于通常涉及熵和焓的大变化的高分子生物分子。熵和焓的不完全消除决定了许多生物物理特征，例如蛋白质热力学稳定性和蛋白质折叠的自由能垒。在这项研究中，我们研究了如何将缀合物与蛋白质连接在一起如何影响蛋白质的热力学稳定性。我们发现共轭物主要通过消除一些残留相互作用的形成而影响未折叠状态。因此，展开状态的焓和熵都受到影响。我们建议，由于这种效应不是局部的，因此构象柔韧性的增益（即例如，增加的熵）大于一些残余相互作用的损失（即增加的焓）。因此，结合蛋白的未折叠状态具有比自由蛋白低的自由能，导致热力学不稳定。