One of the most cited and best methods for prediction of classical signal peptides is the SignalP method [Nielsen et al., 1997,Bendtsen et al., 2004b]. In contrast to other methods, SignalP also predicts the actual cleavage site; thus the peptide which is cleaved off during translocation over the membrane. Recently, an independent research paper has rated SignalP version 3.0 to be the best standalone tool for signal peptide prediction. It was shown that the D-score which is reported by the SignalP method is the best measure for discriminating secretory from non-secretory proteins [Klee and Ellis, 2005].
SignalP is located at http://www.cbs.dtu.dk/services/SignalP/