iAlign: a method for the structural comparison of protein-protein interfaces

Motivation: Protein-protein interactions play an essential role in many cellular processes. The rapid accumulation of protein-protein complex structures provides an unprecedented opportunity for comparative studies of protein-protein interactions. To facilitate such studies, it is necessary to develop an accurate and efficient computational algorithm for the comparison of protein-protein interaction modes. While there are many structural comparison approaches developed for individual proteins, very few methods are available for protein-protein complexes. Results: We present a novel interface alignment method, iAlign, for the structural alignment of protein-protein interfaces. New scoring schemes for measuring interface similarity are introduced, and an iterative dynamic programming algorithm is implemented. We find that the similarity scores follow extreme value distributions. Using statistical models, we empirically estimate their statistical significance, which is in good agreement with manual classifications by human experts. Large-scale tests of iAlign were conducted on both artificial docking models and experimental structures. In a benchmark test on 1517 dimers, iAlign successfully detects biologically related, structurally similar protein-protein interfaces at a coverage percentage of 90% and an error per query of 0.05. When compared against previously published methods, iAlign is substantially more accurate and efficient.