BackgroundTandem repetition of structural motifs in proteins is frequently observed across all forms of life. The topology of the repeating unit and its frequency of occurrence are associated to a wide range of structural and functional roles in diverse proteins, and defects in repeat proteins have been associated with a number of diseases. It is thus desirable to accurately identify the specific repeat type and its copy number. Weak evolutionary constraints on the repeat units and insertions/deletions between them make their identification difficult at the sequence level and structure based approaches are desired. Methods based on periodicity of a signal are affected by insertions/deletions and structure-structure alignment methods are computationally intensive. Thus computationally efficient and effective structure-based approach is desired. The proposed graph theoretic approach based on spectral analysis of protein structure represented as a graph is presented for the identification of one of the most frequently observed structural repeats in proteins, Ankyrin repeat.ResultsIt has been shown in a large number of studies that the 3-dimensional topology of a protein structure is well captured by a graph, making it possible to analyze a complex protein structure as a mathematical entity. In this study we show that the eigen spectra profile of a protein structure graph exhibits a unique repetitive profile for contiguous repeating units enabling the detection of the repeat region and the repeat type. On employing the secondary structure architecture of repeat motifs in known repeat proteins, the prediction accuracy is enhanced. The proposed approach uses a non-redundant set of 58 Ankyrin proteins to define rules for the detection of Ankyrin repeat motifs. The proposed method is evaluated on a set of 370 proteins comprising 125 known Ankyrin proteins and remaining non-solenoid proteins and the prediction compared with UniProt annotation, a sequence-based approach, RADAR, and a structure-based approach, ConSole. To show the efficacy of the approach, we analyzed the complete PDB structural database and identified 641 previously unrecognized Ankyrin repeat proteins. The proposed approach can be easily extended to detect other repeat types as we observe a unique eigen spectra profile for different repeat types. This is shown by considering representative examples from four protein repeat families, viz., Tetratricopeptide repeat (TPR), Armadillo repeat (ARM), Leucine-rich repeat (LRR) and Kelch repeat. The method has been implemented as a web server, called AnkPred. It is freely available at `bioinf.iiit.ac.in/AnkPred¿.ConclusionsAnkPred provides an elegant and computationally efficient graph-based approach for detecting Ankyrin structural repeats in proteins. By analyzing the eigen spectra of the protein structure graph and secondary structure information, characteristic features of a known repeat family are identified with very good accuracy. This method is especially useful in correctly identifying new members of a repeat family. We also show that a number of proteins exhibit multi-repeat architecture that may necessitate the functional analysis of those proteins.