Shen Vincent K, Cheung Jason K, Errington Jeffrey R, Truskett Thomas M
Physical and Chemical Properties Division, National Institute of Standards and Technology, Gaithersburg, MD 20899-8380, USA.
J Biomech Eng. 2009 Jul;131(7):071002. doi: 10.1115/1.3127259.
Proteins aggregate and precipitate from high concentration solutions in a wide variety of problems of natural and technological interest. Consequently, there is a broad interest in developing new ways to model the thermodynamic and kinetic aspects of protein stability in these crowded cellular or solution environments. We use a coarse-grained modeling approach to study the effects of different crowding agents on the conformational equilibria of proteins and the thermodynamic phase behavior of their solutions. At low to moderate protein concentrations, we find that crowding species can either stabilize or destabilize the native state, depending on the strength of their attractive interaction with the proteins. At high protein concentrations, crowders tend to stabilize the native state due to excluded volume effects, irrespective of the strength of the crowder-protein attraction. Crowding agents reduce the tendency of protein solutions to undergo a liquid-liquid phase separation driven by strong protein-protein attractions. The aforementioned equilibrium trends represent, to our knowledge, the first simulation predictions for how the properties of crowding species impact the global thermodynamic stability of proteins and their solutions.
在各种具有自然和技术意义的问题中，蛋白质会从高浓度溶液中聚集并沉淀。因此，人们对开发新方法来模拟这些拥挤的细胞或溶液环境中蛋白质稳定性的热力学和动力学方面有着广泛的兴趣。我们使用粗粒度建模方法来研究不同拥挤剂对蛋白质构象平衡及其溶液热力学相行为的影响。在低至中等蛋白质浓度下，我们发现拥挤物种可以使天然状态稳定或不稳定，这取决于它们与蛋白质的吸引相互作用的强度。在高蛋白质浓度下，由于体积排除效应，拥挤剂倾向于使天然状态稳定，而与拥挤剂 - 蛋白质吸引力的强度无关。拥挤剂降低了蛋白质溶液因强烈的蛋白质 - 蛋白质吸引力而发生液 - 液相分离的趋势。据我们所知，上述平衡趋势代表了关于拥挤物种特性如何影响蛋白质及其溶液的整体热力学稳定性的首次模拟预测。
