Protein-protein association in vivo occur in a crowded and complex environment. Theoretical models based on hard-core repulsion predict stabilization of the product under crowded conditions. Soft interactions, on the contrary, can either stabilize or destabilize the product formation. Here we modeled protein association in presence of crowders of varying size, shape, interaction potential and used different mixing parameters for constituent crowders to study the influence on the association reaction. It was found that size is a more dominant factor in crowder-induced stabilization than the shape. Furthermore, in a mixture of crowders having different sizes but identical interaction potential, the change of free energy is additive of the free energy changes produced by individual crowders. However, the free energy change is not additive if two crowders of same size interact via different interaction potentials. These findings provide a systematic understanding of crowding influences in heterogeneous medium.

体内蛋白质-蛋白质结合发生在拥挤和复杂的环境中。基于硬核排斥的理论模型预测产品在拥挤条件下的稳定性。相反，软相互作用可以稳定或破坏产品的形成。在这里，我们对存在不同大小、形状、相互作用潜力的拥挤物时的蛋白质结合进行建模，并使用不同的混合参数组成拥挤物来研究对缔合反应的影响。发现在拥挤诱导的稳定性中，尺寸比形状更占主导地位。此外，在具有不同尺寸但具有相同相互作用势的拥挤物的混合物中，自由能的变化是由单个拥挤物产生的自由能变化的累加。然而，如果两个大小相同的拥挤物通过不同的相互作用势相互作用，则自由能变化不是相加的。这些发现提供了对异质介质中拥挤影响的系统理解。