Non-native intermolecular contacts often lead to aberrant protein oligomerization and aggregation. This phenomenon is behind the onset of several human disorders and is a bottleneck for the production of proteins of biotechnological interest. Intrinsically disordered proteins have evolved to avoid aberrant oligomerization, but mutations or aging-promoted degeneration of the protein quality machinery might result in their aggregation. Folded globular proteins are not completely protected from aggregation, mostly because the physicochemical properties stabilizing their tertiary and/or quaternary structures are very similar to those leading to non-native oligomerization. Once these properties are known, it becomes feasible to predict the aggregation propensities of proteins and to design them to disfavor aggregation-prone contacts. In this chapter, we describe how computational approaches can assist the identification of the aggregation-prone sequential or structural regions leading to aberrant oligomerization and how these tools can be employed to predict pathogenic mutations or to design biotherapeutics with optimized solubility.

非天然的分子间接触常常导致异常的蛋白质寡聚和聚集。这种现象是几种人类疾病发作的背后原因，并且是产生具有生物技术意义的蛋白质的瓶颈。内在无序的蛋白质已经进化以避免异常的寡聚，但是蛋白质质量机制的突变或老化促进的变性可能导致它们的聚集。折叠的球状蛋白不能完全防止聚集，主要是因为稳定其三级和/或四级结构的物理化学性质与导致非天然寡聚的性质非常相似。一旦知道了这些特性，就可以预测蛋白质的聚集倾向并设计它们以防止易于聚集的接触。在这一章当中，