PPiClust: efficient clustering of 3D protein-protein interaction interfaces

The biological mechanisms through which proteins interact with one another are best revealed by studying the structural interfaces between interacting proteins. Protein-protein interfaces can be extracted from three-dimensional (3D) structural data of protein complexes and then clustered to derive biological insights. However, conventional protein interface clustering methods lack computational scalability and statistical support. In this work, we present a new method named "PPiClust" to systematically encode, cluster, and analyze similar 3D interface patterns in protein complexes efficiently. Experimental results showed that our method is effective in discovering visually consistent and statistically significant clusters of interfaces, and at the same time sufficiently time-efficient to be performed on a single computer. The interface clusters are also useful for uncovering the structural basis of protein interactions. Analysis of the resulting interface clusters revealed groups of structurally diverse proteins having similar interface patterns. We also found, in some of the interface clusters, the presence of well-known linear binding motifs which were noncontiguous in the primary sequences. These results suggest that PPiClust can discover not only statistically significant, but also biologically significant, protein interface clusters from protein complex structural data.