Huang, FeiOldfield, Christopher J.Xue, BinHsu, Wei-LunMeng, JingweiLiu, XiaowenShen, LiRomero, PedroUversky, Vladimir N.Dunker, A. Keith2016-05-252016-05-252014Huang, F., Oldfield, C. J., Xue, B., Hsu, W.-L., Meng, J., Liu, X., … Dunker, A. K. (2014). Improving protein order-disorder classification using charge-hydropathy plots. BMC Bioinformatics, 15(Suppl 17), S4. http://doi.org/10.1186/1471-2105-15-S17-S41471-2105https://hdl.handle.net/1805/9666BACKGROUND: The earliest whole protein order/disorder predictor (Uversky et al., Proteins, 41: 415-427 (2000)), herein called the charge-hydropathy (C-H) plot, was originally developed using the Kyte-Doolittle (1982) hydropathy scale (Kyte & Doolittle., J. Mol. Biol, 157: 105-132(1982)). Here the goal is to determine whether the performance of the C-H plot in separating structured and disordered proteins can be improved by using an alternative hydropathy scale. RESULTS: Using the performance of the CH-plot as the metric, we compared 19 alternative hydropathy scales, with the finding that the Guy (1985) hydropathy scale (Guy, Biophys. J, 47:61-70(1985)) was the best of the tested hydropathy scales for separating large collections structured proteins and intrinsically disordered proteins (IDPs) on the C-H plot. Next, we developed a new scale, named IDP-Hydropathy, which further improves the discrimination between structured proteins and IDPs. Applying the C-H plot to a dataset containing 109 IDPs and 563 non-homologous fully structured proteins, the Kyte-Doolittle (1982) hydropathy scale, the Guy (1985) hydropathy scale, and the IDP-Hydropathy scale gave balanced two-state classification accuracies of 79%, 84%, and 90%, respectively, indicating a very substantial overall improvement is obtained by using different hydropathy scales. A correlation study shows that IDP-Hydropathy is strongly correlated with other hydropathy scales, thus suggesting that IDP-Hydropathy probably has only minor contributions from amino acid properties other than hydropathy. CONCLUSION: We suggest that IDP-Hydropathy would likely be the best scale to use for any type of algorithm developed to predict protein disorder.en-USAttribution 4.0 InternationalAmino AcidschemistryDatabases, ProteinIntrinsically Disordered ProteinsProteinsclassificationConference proceedings