Valle-Orero Jessica, Eckels Edward C, Stirnemann Guillaume, Popa Ionel, Berkovich Ronen, Fernandez Julio M
Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
Biochem Biophys Res Commun. 2015 May 1;460(2):434-8. doi: 10.1016/j.bbrc.2015.03.051. Epub 2015 Mar 18.
Recent studies have provided a theoretical framework for including entropic elasticity in the free energy landscape of proteins under mechanical force. Accounting for entropic elasticity using polymer physics models has helped explain the hopping behavior seen in single molecule experiments in the low force regime. Here, we expand on the construction of the free energy of a single protein domain under force proposed by Berkovich et al. to provide a free energy landscape for N tandem domains along a continuous polypeptide. Calculation of the free energy of individual domains followed by their concatenation provides a continuous free energy landscape whose curvature is dominated by the worm-like chain at forces below 20 pN. We have validated our free energy model using Brownian dynamics and reproduce key features of protein folding. This free energy model can predict the effects of changes in the elastic properties of a multidomain protein as a consequence of biological modifications such as phosphorylation or the formation of disulfide bonds. This work lays the foundations for the modeling of tissue elasticity, which is largely determined by the properties of tandem polyproteins.
最近的研究为在机械力作用下将熵弹性纳入蛋白质的自由能景观提供了理论框架。使用聚合物物理模型考虑熵弹性有助于解释在低力 regime 下单分子实验中观察到的跳跃行为。在此，我们扩展了 Berkovich 等人提出的在力作用下单蛋白质结构域自由能的构建，以提供沿连续多肽的 N 个串联结构域的自由能景观。通过计算各个结构域的自由能然后将它们连接起来，得到了一个连续的自由能景观，其曲率在低于 20 pN 的力下由类蠕虫链主导。我们使用布朗动力学验证了我们的自由能模型，并重现了蛋白质折叠的关键特征。这种自由能模型可以预测由于生物修饰（如磷酸化或二硫键形成）导致的多结构域蛋白质弹性特性变化的影响。这项工作为组织弹性建模奠定了基础，组织弹性在很大程度上由串联多聚蛋白的特性决定。
