Publications

Prediction of β-strand packing interactions using the signature product

Brown, W.M.; Martin, Shawn; Chabarek, Joseph P.; Strauss, Charlie; Faulon, Jean-Loup M.

The prediction of β-sheet topology requires the consideration of long-range interactions between β-strands that are not necessarily consecutive in sequence. Since these interactions are difficult to simulate using ab initio methods, we propose a supplementary method able to assign β-sheet topology using only sequence information. We envision using the results of our method to reduce the three-dimensional search space of ab initio methods. Our method is based on the signature molecular descriptor, which has been used previously to predict protein-protein interactions successfully, and to develop quantitative structure-activity relationships for small organic drugs and peptide inhibitors. Here, we show how the signature descriptor can be used in a Support Vector Machine to predict whether or not two β-strands will pack adjacently within a protein. We then show how these predictions can be used to order β-strands within β-sheets. Using the entire PDB database with ten-fold cross-validation, we have achieved 74.0% accuracy in packing prediction and 75.6% accuracy in the prediction of edge strands. For the case of β-strand ordering, we are able to predict the correct ordering accurately for 51.3% of the β-sheets. Furthermore, using a simple confidence metric, we can determine those sheets for which accurate predictions can be obtained. For the top 25% highest confidence predictions, we are able to achieve 95.7% accuracy in β-strand ordering. © Springer-Verlag 2005.