SeqFold – fully automated fold recognition and modeling software – evaluation and application

Abstract.

SeqFold is a fold recognition program based on sequence-similarity detection aided by predicted secondary structure [1–3]. Critical validation and evaluation of SeqFold fold recognition performance based on the latest Critical Assessment of protein Structure Prediction (CASP2) targets has been performed. It has revealed that four out of seven CASP2 threading targets were assigned a correct fold using this method. SeqFold has also been applied to the problem of fold recognition for leptin. Mice with a defective leptin gene are extremely obese and diabetic. Leptin does not exhibit clear sequence homology to any protein with known structure. SeqFold predicts that leptin belongs to the class of short-chain four-helical cytokines. The structure of leptin, which has recently been solved by X-ray crystallography, reveals that leptin is a long-chain four-helical cytokine. The 3D model of leptin demonstrates that SeqFold alignment-based homology modeling captures essential features of the leptin structure.