Cheung Jason K, Shen Vincent K, Errington Jeffrey R, Truskett Thomas M
Department of Chemical Engineering, The University of Texas at Austin, Austin, Texas, USA.
Biophys J. 2007 Jun 15;92(12):4316-24. doi: 10.1529/biophysj.106.099085. Epub 2007 Mar 30.
We extend our coarse-grained modeling strategy described in parts I and II of this investigation to account for nonuniform spatial distributions of hydrophobic residues on the solvent-exposed surfaces of native proteins. Within this framework, we explore how patchy surfaces can influence the solvent-mediated protein-protein interactions, and the unfolding and self-assembly behaviors of proteins in solution. In particular, we compare the equilibrium unfolding and self-assembly trends for three model proteins that share the same overall sequence hydrophobicity, but exhibit folded configurations with different solvent-exposed native-state surface morphologies. Our model provides new insights into how directional interactions can affect native-state protein stability in solution. We find that strongly-directional attractions between native molecules with patchy surfaces can help stabilize the folded conformation through the formation of self-assembled clusters. In contrast, native proteins with more uniform surfaces are destabilized by protein-protein attractions involving the denatured state. Finally, we discuss how the simulation results provide insights into the experimental solution behaviors of several proteins that display directional interactions in their native states.
我们将本研究第一部分和第二部分中描述的粗粒度建模策略进行扩展，以考虑天然蛋白质溶剂暴露表面上疏水残基的非均匀空间分布。在此框架内，我们探讨了斑块状表面如何影响溶剂介导的蛋白质-蛋白质相互作用，以及溶液中蛋白质的去折叠和自组装行为。特别地，我们比较了三种模型蛋白质的平衡去折叠和自组装趋势，这三种蛋白质具有相同的整体序列疏水性，但呈现出具有不同溶剂暴露天然态表面形态的折叠构象。我们的模型为定向相互作用如何影响溶液中天然态蛋白质稳定性提供了新的见解。我们发现，具有斑块状表面的天然分子之间的强定向吸引力可通过形成自组装簇来帮助稳定折叠构象。相比之下，表面更均匀的天然蛋白质会因涉及变性态的蛋白质-蛋白质吸引力而变得不稳定。最后，我们讨论了模拟结果如何为几种在天然状态下显示定向相互作用的蛋白质的实验溶液行为提供见解。
