Virtual interaction profiles of proteins

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.