Outline of D-MIST Method for Predicting Protein Interactions by Learned Binding Profiles

Identification of domain-binding profiles begins by extracting the short sequence motifs from structural complexes that contain the domain of interest.

(A) In this example, RhoGAP-interacting motifs are extracted from two structural complexes (PDB ID 1AM4, 1TX4) where RhoGAP is bound to small G proteins.

(B) Protein interactions containing the RhoGAP domain were collected from four databases to form the learning set for the Gibbs sampling to generate the binding profiles (shown here as sequence logos [57]). The sampling step is biased towards motifs that are similar to those found in the structural dataset.

(C) The resulting PSSMs are used to predict interactions for proteins with RhoGAP domains, such as the human ARHGAP1. A subset of the predicted interactions is subsequently tested by two experimental methods.