Sealy Center for Structural Biology and Molecular Biophysics, The University of Texas Medical Branch, Galveston, Texas.
Sealy Center for Structural Biology and Molecular Biophysics, The University of Texas Medical Branch, Galveston, Texas.
Biophys J. 2018 Jun 19;114(12):2799-2810. doi: 10.1016/j.bpj.2018.04.027.
Conformational entropy is expected to contribute significantly to the thermodynamics of structural transitions in intrinsically disordered proteins or regions in response to protein/ligand binding, posttranslational modifications, and environmental changes. We calculated the backbone (dihedral) conformational entropy of oligoglycine (Gly), a protein backbone mimic and model intrinsically disordered region, as a function of chain length (N=3, 4, 5, 10, and 15) from simulations using three different approaches. The backbone conformational entropy scales linearly with chain length with a slope consistent with the entropy of folding of well-structured proteins. The entropic contributions of second-order dihedral correlations are predominantly through intraresidue ϕ-ψ pairs, suggesting that oligoglycine may be thermodynamically modeled as a system of independent glycine residues. We find the backbone conformational entropy to be largely independent of global structural parameters, like the end-to-end distance and radius of gyration. We introduce a framework referred to herein as "ensemble confinement" to estimate the loss (gain) of conformational free energy and its entropic component when individual residues are constrained to (released from) particular regions of the ϕ-ψ map. Quantitatively, we show that our protein backbone model resists ordering/folding with a significant, unfavorable ensemble confinement free energy because of the loss of a substantial portion of the absolute backbone entropy. Proteins can couple this free-energy reservoir to distal binding events as a regulatory mechanism to promote or suppress binding.
构象熵有望对无规卷曲蛋白质或区域的结构转变热力学产生重大影响，这些转变是响应蛋白质/配体结合、翻译后修饰和环境变化而发生的。我们计算了寡聚甘氨酸（Gly）的主链（二面角）构象熵，这是一种蛋白质主链模拟物和无规卷曲区域模型，作为模拟的函数，模拟使用了三种不同的方法，链长（N=3、4、5、10 和 15）。主链构象熵与链长呈线性关系，斜率与结构良好蛋白质的折叠熵一致。二阶二面角相关的熵贡献主要通过残基内的 ϕ-ψ 对，这表明寡聚甘氨酸可能可以被热力学模拟为独立甘氨酸残基的系统。我们发现主链构象熵在很大程度上独立于全局结构参数，如末端到末端的距离和回转半径。我们引入了一个称为“集合限制”的框架，以估计当单个残基被限制（释放）到 ϕ-ψ 图谱的特定区域时，构象自由能及其熵分量的损失（获得）。定量地，我们表明我们的蛋白质主链模型由于绝对主链熵的大量损失而抵抗有序/折叠，这是由于集合限制自由能的显著不利。蛋白质可以将这个自由能库与远距离结合事件耦合，作为促进或抑制结合的调节机制。
