DNA-binding proteins perform vital functions related to transcription, repair and replication. We have developed a new sequence-based machine learning protocol to identify DNA-binding proteins. We compare our method with an extensive benchmark of previously published structure-based machine learning methods as well as a standard sequence alignment technique, BLAST. Furthermore, we elucidate important feature interactions found in a learned model and analyze how specific rules capture general mechanisms that extend across DNA-binding motifs. This analysis is carried out using the malibu machine learning workbench available at http://proteomics.bioengr.uic.edu/malibu and the corresponding data sets and features are available at http://proteomics.bioengr.uic.edu/dna.