Department of Chemistry and Theoretical Chemistry Institute, University of Wisconsin, Madison, Wisconsin 53706, USA.
J Phys Chem B. 2011 Jan 20;115(2):347-53. doi: 10.1021/jp107123y. Epub 2010 Dec 17.
The cell cytoplasm is a dense environment where the presence of inert cosolutes can significantly alter the rates of protein folding and protein association reactions. Most theoretical studies focus on hard sphere crowding agents and quantify the effect of excluded volume on reaction rates. In this work the effect of interactions between the crowding agents on the thermodynamics of protein association is studied using computer simulation. Three cases are considered, where the crowding agents are (i) hard spheres, (ii) hard spheres with additional attractive or repulsive interactions, and (iii) chains of hard spheres. Reactants and products of the protein association are modeled as hard spheres. Although crowding effects are sensitive to the shape of the reaction product, in most cases the excess free energy difference between the product and reactants (nonideality factor) is insensitive to the interactions between crowding agents, due to a cancellation of effects. The simulations therefore suggest that the hard sphere model of crowding agents has a surprisingly large regime of validity and should be sufficient for a qualitative understanding of the thermodynamics of crowding effects when the interactions of associating proteins with crowding agents other than excluded volume interactions are not significant.
细胞质是一个密集的环境，其中惰性共溶剂的存在会显著改变蛋白质折叠和蛋白质缔合反应的速率。大多数理论研究集中在硬球拥挤剂上，并量化了排斥体积对反应速率的影响。在这项工作中，使用计算机模拟研究了拥挤剂之间相互作用对蛋白质缔合热力学的影响。考虑了三种情况，其中拥挤剂为（i）硬球，（ii）具有附加吸引力或排斥力的硬球，以及（iii）硬球链。蛋白质缔合的反应物和产物被建模为硬球。尽管拥挤效应对反应产物的形状敏感，但在大多数情况下，产物和反应物之间的过剩自由能差（非理想因子）对拥挤剂之间的相互作用不敏感，因为相互作用的影响相互抵消。因此，模拟表明，拥挤剂的硬球模型具有惊人的大范围有效性，并且在与除排斥体积相互作用之外的拥挤剂相互作用的缔合蛋白质的相互作用不显著时，对于定性理解拥挤效应的热力学应该足够了。
