title: Virtual interaction profiles of proteins.
abstract: We have developed a new method for the prediction of peptide sequences that bind to a protein, given a three-dimensional structure of the protein in complex with a peptide. By applying a recently developed sequence prediction algorithm and a novel ensemble averaging calculation, we generate a diverse collection of peptide sequences that are predicted to have significant affinity for the protein. Using output from the simulations, we create position-specific scoring matrices, or virtual interaction profiles (VIPs). Comparison of VIPs for a collection of binding motifs to sequences determined experimentally indicates that the prediction algorithm is accurate and applicable to a diverse range of structures. With these VIPs, one can scan protein sequence databases rapidly to seek binding partners of potential biological significance. Overall, this method can significantly enhance the information contained within a protein- peptide crystal structure, and enrich the data obtained by experimental selection methods such as phage display.
authors.affiliation: Department of Chemistry, Pennsylvania State University, 406 Chandlee Laboratory, PA 16802, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Wollacott
authors.forename: J R
authors.initials: JR
authors.lastname: Desjarlais
mesh_terms: D000465:Algorithms; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D030562:Databases, Protein; D051528:Guanylate Kinases; D000072233:Homer Scaffolding Proteins; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D009479:Neuropeptides / Q000737:chemistry / Q000378:metabolism; D009687:Nuclear Proteins; D009703:Nucleoside-Phosphate Kinase / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods*; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism; D016315:Proto-Oncogene Proteins c-abl / Q000737:chemistry / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn; D051736:Proto-Oncogene Proteins c-mdm2; D012680:Sensitivity and Specificity; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013816:Thermodynamics; D018909:src Homology Domains
chemical_list: D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D009687:Nuclear Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; C033652:postsynaptic density proteins; C497206:MDM2 protein, human; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2; C494957:FYN protein, human; C494960:Fyn protein, mouse; D016315:Proto-Oncogene Proteins c-abl; D051076:Proto-Oncogene Proteins c-fyn; C106868:CASK kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases