Computational tools to predict context-specific protein complexes

Interactions between thousands of proteins define cells' protein–protein interaction (PPI) network. Some of these interactions lead to the formation of protein complexes. It is challenging to identify a protein complex in a haystack of protein–protein interactions, and it is even more difficult to predict all protein complexes of the complexome. Simulations and machine learning approaches try to crack these problems by looking at the PPI network or predicted protein structures. Clustering of PPI networks led to the first protein complex predictions, while most recently, atomistic models of protein complexes and deep-learning-based structure prediction methods have also emerged. The simulation of PPI level interactions even enables the quantitative prediction of protein complexes. These methods, the required data sources, and their potential future developments are discussed in this review.