Patro S Y, Przybycien T M
Howard P. Isermann Department of Chemical Engineering, Rensselaer Polytechnic Institute, Troy, New York 12180-3590, USA.
Biophys J. 1996 Jun;70(6):2888-902. doi: 10.1016/S0006-3495(96)79859-4.
We simulated the structure of reversible protein aggregates as a function of protein surface characteristics, protein-protein interaction energies, and the entropic penalty accompanying the immobilization of protein in a solid phase. These simulations represent an extension of our previous work on kinetically irreversible protein aggregate structure and are based on an explicit accounting of the specific protein-protein interactions that occur within reversible aggregates and crystals. We considered protein monomers with a mixture of hydrophobic and hydrophilic surface regions suspended in a polar solvent; the energetic driving force for aggregation is provided by the burial of solvent-exposed hydrophobic surface area. We analyzed the physical properties of the generated aggregates, including density, protein-protein contact distributions, solvent accessible surface area, porosity, and order, and compared our results with the protein crystallization literature as well as with the kinetically irreversible case. The physical properties of reversible aggregates were consonant with those observed for the irreversible aggregates, although in general, reversible aggregates were more stable energetically and were more crystal-like in their order content than their irreversible counterparts. The reversible aggregates were less dense than the irreversible aggregates, indicating that the increased energetic stability is derived primarily from the optimality rather than the density of the packing in the solid phase. The extent of hydrophobic protein-protein contacts and solvent-exposed surface area within the aggregate phase depended on the aggregation pathway: reversible aggregates tended to have a greater proportion of hydrophobic-hydrophobic contacts and a smaller fraction of hydrophobic solvent-exposed surface area. Furthermore, the arrangement of hydrophobic patches on the protein surface played a major role in the distribution of protein contacts and solvent content. This was readily reflected in the order of the aggregates: the greater the contiguity of the hydrophobic patches on the monomer surface, the less ordered the aggregates became, despite the opportunities for rearrangement offered by a reversible pathway. These simulations have enhanced our understanding of the impact of protein structural motifs on aggregate properties and on the demarcation between aggregation and crystallization.
我们模拟了可逆蛋白质聚集体的结构，该结构是蛋白质表面特征、蛋白质 - 蛋白质相互作用能以及蛋白质固定在固相中所伴随的熵罚的函数。这些模拟是我们之前关于动力学不可逆蛋白质聚集体结构工作的扩展，并且基于对可逆聚集体和晶体中发生的特定蛋白质 - 蛋白质相互作用的明确计算。我们考虑了具有疏水和亲水表面区域混合的蛋白质单体悬浮在极性溶剂中；聚集的能量驱动力由溶剂暴露的疏水表面积的埋藏提供。我们分析了生成的聚集体的物理性质，包括密度、蛋白质 - 蛋白质接触分布、溶剂可及表面积、孔隙率和有序度，并将我们得到的结果与蛋白质结晶文献以及动力学不可逆情况进行了比较。可逆聚集体的物理性质与不可逆聚集体所观察到的性质一致，尽管一般来说，可逆聚集体在能量上更稳定，并且在有序度方面比其不可逆对应物更像晶体。可逆聚集体的密度低于不可逆聚集体，这表明能量稳定性的增加主要源于固相堆积的最优性而非密度。聚集体相内疏水蛋白质 - 蛋白质接触的程度和溶剂暴露表面积取决于聚集途径：可逆聚集体倾向于具有更大比例的疏水 - 疏水接触和更小比例的疏水溶剂暴露表面积。此外，蛋白质表面疏水斑块的排列在蛋白质接触和溶剂含量的分布中起主要作用。这很容易在聚集体的有序度中体现出来：单体表面疏水斑块的连续性越大，聚集体的有序度就越低，尽管可逆途径提供了重排的机会。这些模拟增强了我们对蛋白质结构基序对聚集体性质以及聚集与结晶界限影响的理解。
