Computational approaches to identify leucine zippers

The leucine zipper is a dimerization domain occurring mostly in regulatory and thus in many oncogenic proteins. The leucine repeat in the sequence has been traditionally used for identification, however with poor reliability. The coiled coil structure of a leucine zipper is required for dimerization and can be predicted with reasonable accuracy by existing algorithms. We exploit this fact for identification of leucine zippers from sequence alone. We present a program, 2ZIP, which combines a standard coiled coil prediction algorithm with an approximate search for the characteristic leucine repeat. No further information from homologues is required for prediction. This approach improves significantly over existing methods, especially in that the coiled coil prediction turns out to be highly informative and avoids large numbers of false positives. Many problems in predicting zippers or assessing prediction results stem from wrong sequence annotations in the database.