Critical evaluation of in silico methods for prediction of coiled-coil domains in proteins

Chen Li, Catherine C H Chang, Jeremy M Nagel, Ben T Porebski, Morihiro Hayashida, Tatsuya Akutsu, Jiangning Song, Ashley M Buckle

Research output: Contribution to journalArticleResearchpeer-review

18 Citations (Scopus)


Coiled-coils refer to a bundle of helices coiled together like strands of a rope. It has been estimated that nearly 3 of protein-encoding regions of genes harbour coiled-coil domains (CCDs). Experimental studies have confirmed that CCDs play a fundamental role in subcellular infrastructure and controlling trafficking of eukaryotic cells. Given the importance of coiled-coils, multiple bioinformatics tools have been developed to facilitate the systematic and high-throughput prediction of CCDs in proteins. In this article, we review and compare 12 sequence-based bioinformatics approaches and tools for coiled-coil prediction. These approaches can be categorized into two classes: coiled-coil detection and coiled-coil oligomeric state prediction. We evaluated and compared these methods in terms of their input/output, algorithm, prediction performance, validation methods and software utility. All the independent testing data sets are available at In addition, we conducted a case study of nine human polyglutamine (PolyQ) disease-related proteins and predicted CCDs and oligomeric states using various predictors. Prediction results for CCDs were highly variable among different predictors. Only two peptides from two proteins were confirmed to be CCDs by majority voting. Both domains were predicted to form dimeric coiled-coils using oligomeric state prediction. We anticipate that this comprehensive analysis will be an insightful resource for structural biologists with limited prior experience in bioinformatics tools, and for bioinformaticians who are interested in designing novel approaches for coiled-coil and its oligomeric state prediction.
Original languageEnglish
Pages (from-to)270 - 282
Number of pages13
JournalBriefings in Bioinformatics
Issue number2
Publication statusPublished - 2016

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