Improving the quality of co-evolution intermolecular contact prediction with DisVis.

Abstract

The steep rise in protein sequences and structures has paved the way for bioinformatics approaches to predict residue-residue interactions in protein complexes. Multiple sequence alignments are commonly used in contact predictions to identify co-evolving residues. These contacts, however, often include false positives (FPs), which may impair their use to predict three dimensional structures of biomolecular complexes and affect the accuracy of the generated models. Previously, we have developed DisVis to identify FP in mass spectrometry cross-linking data. DisVis allows to assess the accessible interaction space between two proteins consistent with a set of distance restraints. Here, we investigate if a similar approach could be applied to co-evolution predicted contacts in order to improve their precision prior to using them for modeling. We analyze co-evolution contact predictions with DisVis for a set of 26 protein-protein complexes. The DisVis-reranked and the original co-evolution contacts are then used to model the complexes with our integrative docking software HADDOCK using different filtering scenarios. Our results show that HADDOCK is robust with respect to the precision of the predicted contacts due to the 50% random contact removal during docking and can enhance the quality of docking predictions when combined with DisVis filtering for low precision contact data. DisVis can thus have a beneficial effect on low quality data, but overall HADDOCK can accommodate FP restraints without negatively impacting the quality of the resulting models. Other more precision-sensitive docking protocols might, however, benefit from the increased precision of the predicted contacts after DisVis filtering.