A neural network method for prediction of β-turn types in proteins using evolutionary information

Abstract

Motivation: The prediction of β-turns is an important element of protein secondary structure prediction. Recently, a highly accurate neural network based method Betatpred2 has been developed for predicting β-turns in proteins using position-specific scoring matrices (PSSM) generated by PSI-BLAST and secondary structure information predicted by PSIPRED. However, the major limitation of Betatpred2 is that it predicts only β-turn and non-β-turn residues and does not provide any information of different β-turn types. Thus, there is a need to predict β-turn types using an approach based on multiple sequence alignment, which will be useful in overall tertiary structure prediction. Results: In the present work, a method has been developed for the prediction of β-turn types I, II, IV and VIII. For each turn type, two consecutive feed-forward back-propagation networks with a single hidden layer have been used where the first sequence-to-structure network has been trained on single sequences as well as on PSI-BLAST PSSM. The output from the first network along with PSIPRED predicted secondary structure has been used as input for the second-level structure-to-structure network. The networks have been trained and tested on a non-homologous dataset of 426 proteins chains by 7-fold cross-validation. It has been observed that the prediction performance for each turn type is improved significantly by using multiple sequence alignment. The performance has been further improved by using a second level structure-to-structure network and PSIPRED predicted secondary structure information. It has been observed that Type I and II β-turns have better prediction performance than Type IV and VIII β-turns. The final network yields an overall accuracy of 74.5, 93.5, 67.9 and 96.5% with MCC values of 0.29, 0.29, 0.23 and 0.02 for Type I, II, IV and VIII β-turns, respectively, and is better than random prediction. Availability: A web server for prediction of β-turn types I, II, IV and VIII based on above approach is available at http://www.imtech.res.in/raghava/betaturns/ and http://bioinformatics.uams.edu/mirror/betaturns/ (mirror site).