AbstractFold recognition predicts protein three‐dimensional structure by establishing relationships between a protein sequence and known protein structures. Most methods explicitly use information derived from the secondary and tertiary structure of the templates. Here we show that rigorous application of a sequence search method (PSI‐BLAST) with no reference to secondary or tertiary structure information is able to perform as well as traditional fold recognition methods. Since the method, SENSER, does not require knowledge of the three‐dimensional structure, it can be used to infer relationships that are not tractable by methods dependent on structural templates.