The document discusses using structural information to predict protein-protein interaction and enzyme specificity. It describes a method for predicting peptide specificity of protein kinases by identifying key sequence residues, querying databases for similar kinases and known substrates, building scoring matrices from peptides, and evaluating prediction scores against other tools. The approach has been applied to CMGC kinases and could potentially be automated and expanded to other protein-peptide recognition systems given sufficient structural data.

1. Structure, interaction and peptide specificity Using Structural Information To Predict Protein-Protein Interaction And Enzyme Specificity Neil Saunders , Thomas Huber, Bostjan Kobe School of Molecular and Microbial Sciences The University of Queensland http://predikin.biosci.uq.edu.au

2. Structure, interaction and peptide specificity Peptide specificity of protein kinases CK-2 PKA MAPK kinase ATP protein OH + protein O-P i kinase ADP +

3. Structure, interaction and peptide specificity Structural basis for peptide specificity PKA surface + heptapeptide RRA S IHD Schematic of heptapeptide + PKA SDRs

4. Structure, interaction and peptide specificity 1. Identify key sequence residues reference *->Yellkkl GkG aFGkVylardkktgrlv AiK vik..........eril Y+++k+lG+G+FGkV+la+++ tg++vA+K+i+++ +++ + ri+ query 55 YQIVKTL GE GS F GKVKLAYHTTTGQKV ALK IINkkvl aks dmqGRIE 101 -1 +2 X X X [ST] X X X Prediction of peptide specificity from sequence kinase substrate

5. Structure, interaction and peptide specificity 2. Query a database for similar protein kinases Q FS T VKG E QF S TVK R SV S EAA R SG S SPN R HD S GLD R RM S DEF A RG S FDA Query kinase kinases substrates sites

7. Structure, interaction and peptide specificity 4. Evaluate scores serine/threonine CMGC Predikin (SDR) 0.86 (0.04) 0.93 (0.02) GPS 0.83 0.94 KinasePhos 0.78 0.95 NetPhosK 0.90 0.57 PPSP 0.92 0.95 Scansite 0.95 0.94 ROC curve, CMGC kinases, Predikin SDR AROC values, Predikin v. competition

8. Structure, interaction and peptide specificity 5. Publish! Nucleic Acid Res. 36: W286-W290 (2008) BMC Bioinformatics 9: 245 (2008)

10. Structure, interaction and peptide specificity 1. A more automated workflow Less visual inspection More computed analyses Queries Predictions Protein-peptide structures Define key contacts Database Models

12. Structure, interaction and peptide specificity 3. Data curation and visualisation Model organisms kinases substrates sites queries visualisation prediction annotation