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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Assessing the solvent-dependent surface area of unfolded proteins using an ensemble model
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Assessing the solvent-dependent surface area of unfolded proteins using an ensemble model

机译：使用集成模型评估未折叠蛋白质的溶剂依赖性表面积

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摘要

We present a physically rigorous method to calculate solvent-dependent accessible surface areas (ASAs) of amino acid residues in unfolded proteins. ASA values will be larger in a good solvent, where solute-solvent interactions dominate and promote chain extension. Conversely, they will be smaller in a poor solvent, where solute-solute interactions dominate and promote chain collapse. In the method described here, these solvent-dependent effects are modeled by Boltzmann-weighting a simulated ensemble for solvent quality—good or poor. Solvent quality is parameterized as intramolecular hydrogen bond strength, using a "hydrogen bond dial" that can be varied from "off" to "high" (i.e., from 0 to -6 kcal/mol per hydrogen bond). When plotted as a function of hydrogen bond strength, the Boltzmann-weighted distribution of conformers describes a sigmoidal curve, with a transition midpoint near 1.5 kcal/mol per hydrogen bond. ASA tables for the 20 residues are provided under good solvent conditions and at this transition midpoint. For the backbone, these midpoint ASA values are found to be in good agreement with the earlier estimate of unfolded state ASA given by the mean of Creamer's upper and lower bounds [Creamer TP, et al. (1997) Biochemistry 36:2832-2835], a gratifying result in that cosolvents of experimental interest, such as urea (good solvent) and trimethylamine N-oxide (poor solvent), are known to affect the backbone predominantly. Unanticipated results from our simulations predict that a significant population of three-residue, hydrogen-bonded turns (inverse γ-turns) will be detectable in blocked polyalanyl heptamers in poor solvent—an experimentally verifiable conjecture.
机译：我们提出了一种严格的物理方法来计算未折叠蛋白质中氨基酸残基的溶剂依赖性可及表面积（ASAs）。在良好的溶剂中，溶质-溶剂相互作用起主导作用并促进链扩展，ASA值将更大。相反，在不良溶剂中溶质与溶质的相互作用占主导，并促进链塌陷，它们的体积会变小。在此处描述的方法中，这些与溶剂有关的效应通过Boltzmann加权对溶剂质量（好或坏）的模拟集合进行建模。使用“氢键标度”将溶剂质量参数化为分子内氢键强度，该氢键标度可以从“关闭”变为“高”（即，每个氢键从0至-6kcal / mol）。当绘制为氢键强度的函数时，构象异构体的玻尔兹曼加权分布描述为S形曲线，每个氢键的过渡中点接近1.5 kcal / mol。在良好的溶剂条件下和此过渡中点提供了20种残留物的ASA表。对于骨干，发现这些中点ASA值与Creamer上下限的平均值给出的对未折叠状态ASA的早期估计非常吻合[Creamer TP等。 （1997）Biochemistry 36：2832-2835]，这是令人满意的结果，已知实验上感兴趣的助溶剂，例如尿素（良好的溶剂）和三甲胺N-氧化物（不良的溶剂），主要影响骨架。我们的模拟结果出乎意料，结果预测，在不良溶剂中，封端的聚丙氨酰七聚体将可检测到大量的三个残基，氢键合的匝（反向γ匝），这是一个实验可验证的推测。

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