Carmichael Scott P, Shell M Scott
Department of Chemical Engineering, University of California Santa Barbara, Santa Barbara, California 93106, USA.
J Chem Phys. 2015 Dec 28;143(24):243103. doi: 10.1063/1.4929592.
In many emerging biotechnologies, functional proteins must maintain their native structures on or near interfaces (e.g., tethered peptide arrays, protein coated nanoparticles, and amphiphilic peptide micelles). Because the presence of a surface is known to dramatically alter the thermostability of tethered proteins, strategies to stabilize surface-bound proteins are highly sought. Here, we show that polymer conjugation allows for significant control over the secondary structure and thermostability of a model surface-tethered peptide. We use molecular dynamics simulations to examine the folding behavior of a coarse-grained helical peptide that is conjugated to polymers of various lengths and at various conjugation sites. These polymer variations reveal surprisingly diverse behavior, with some stabilizing and some destabilizing the native helical fold. We show that ideal-chain polymer entropies explain these varied effects and can quantitatively predict shifts in folding temperature. We then develop a generic theoretical model, based on ideal-chain entropies, that predicts critical lengths for conjugated polymers to effect changes in the folding of a surface-bound protein. These results may inform new design strategies for the stabilization of surface-associated proteins important for a range technological applications.
在许多新兴生物技术中，功能蛋白必须在界面上或其附近维持其天然结构（例如， tethered肽阵列、蛋白质包被的纳米颗粒和两亲性肽胶束）。由于已知表面的存在会显著改变 tethered蛋白的热稳定性，因此人们一直在大力寻求稳定表面结合蛋白的策略。在这里，我们表明聚合物共轭能够对模型表面 tethered肽的二级结构和热稳定性进行显著控制。我们使用分子动力学模拟来研究与不同长度和不同共轭位点的聚合物共轭的粗粒化螺旋肽的折叠行为。这些聚合物变化揭示了惊人的多样行为，一些使天然螺旋折叠稳定，一些则使其不稳定。我们表明理想链聚合物熵可以解释这些不同的影响，并能定量预测折叠温度的变化。然后，我们基于理想链熵开发了一个通用理论模型，该模型预测共轭聚合物影响表面结合蛋白折叠变化的临界长度。这些结果可能为稳定对一系列技术应用重要的表面相关蛋白的新设计策略提供信息。
