Preference functions for prediction of membrane-buried helices in integral membrane proteins

Abstract

The preference functions method is described for prediction of membrane-buried helices in membrane proteins. Preference for the α-helix conformation of amino acid residue in a sequence is a non-linear function of average hydrophobicity of its sequence neighbors. Kyte–Doolittle hydropathy values are used to extract preference functions from a training data set of integral membrane proteins of partially known secondary structure. Preference functions for β-sheet, turn and undefined conformation are also extracted by including β-class soluble proteins of known structure in the training data set. Conformational preferences are compared in tested sequence for each residue and predicted secondary structure is associated with the highest preference. This procedure is incorporated in an algorithm that performs accurate prediction of transmembrane helical segments. Correct sequence location and secondary structure of transmembrane segments is predicted for 20 of 21 reference membrane polypeptides with known crystal structure that were not included in the training data set. Comparison with hydrophobicity plots revealed that our preference profiles are more accurate and exhibit higher resolution and less noise. Shorter unstable or movable membrane-buried α-helices are also predicted to exist in different membrane proteins with transport function. For instance, in the sequence of voltage-gated ion channels and glutamate receptors, N-terminal parts of known P-segments can be located as characteristic α-helix preference peaks. Our e-mail server: predict@drava.etfos.hr, returns a preference profile and secondary structure prediction for a suspected or known membrane protein when its sequence is submitted.