Fold assignments for proteins from the Escherichia coli genome are carried out using BASIC, a profile–profile alignment algorithm, recently tested on fold recognition benchmarks and on the Mycoplasma genitalium genome and PSI BLAST, the newest generation of the de facto standard in homology search algorithms. The fold assignments are followed by automated modeling and the resulting three-dimensional models are analyzed for possible function prediction.

Close to 30% of the proteins encoded in the E. coli genome can be recognized as homologous to a protein family with known structure. Most of these homologies (23% of the entire genome) can be recognized both by PSI BLAST and BASIC algorithms, but the latter recognizes an additional 260 homologies. Previous estimates suggested that only 10–15% of E. coli proteins can be characterized this way. This dramatic increase in the number of recognized homologies between E. coli proteins and structurally characterized protein families is partly due to the rapid increase of the database of known protein structures, but mostly it is due to the significant improvement in prediction algorithms.

Knowing protein structure adds a new dimension to our understanding of its function and the predictions presented here can be used to predict function for uncharacterized proteins. Several examples, analyzed in more detail in this paper, include the DPS protein protecting DNA from oxidative damage (predicted to be homologous to ferritin with iron ion acting as a reducing agent) and the ahpC/tsa family of proteins, which provides resistance to various oxidating agents (predicted to be homologous to glutathione peroxidase).