title: Prediction of cis/trans isomerization using feature selection and support vector machines.
abstract: In protein structures the peptide bond is found to be in trans conformation in the majority of the cases. Only a small fraction of peptide bonds in proteins is reported to be in cis conformation. Most of these instances (>90%) occur when the peptide bond is an imide (X-Pro) rather than an amide bond (X-nonPro). Due to the implication of cis/trans isomerization in many biologically significant processes, the accurate prediction of the peptide bond conformation is of high interest. In this study, we evaluate the effect of a wide range of features, towards the reliable prediction of both proline and non-proline cis/trans isomerization. We use evolutionary profiles, secondary structure information, real-valued solvent accessibility predictions for each amino acid and the physicochemical properties of the surrounding residues. We also explore the predictive impact of a modified feature vector, which consists of condensed position-specific scoring matrices (PSSMX), secondary structure and solvent accessibility. The best discriminating ability is achieved using the first feature vector combined with a wrapper feature selection algorithm and a support vector machine (SVM). The proposed method results in 70% accuracy, 75% sensitivity and 71% positive predictive value (PPV) in the prediction of the peptide bond conformation between any two amino acids. The output of the feature selection stage is investigated in order to identify discriminatory features as well as the contribution of each neighboring residue in the formation of the peptide bond, thus, advancing our knowledge towards cis/trans isomerization.
authors.affiliation: Unit of Medical Technology and Intelligent Information Systems, Department of Computer Science, University of Ioannina, P.O. Box 1186, GR 45110 Ioannina, Greece.
authors.forename: Konstantinos P
authors.initials: KP
authors.lastname: Exarchos
authors.forename: Costas
authors.initials: C
authors.lastname: Papaloukas
authors.forename: Themis P
authors.initials: TP
authors.lastname: Exarchos
authors.forename: Anastassios N
authors.initials: AN
authors.lastname: Troganis
authors.forename: Dimitrios I
authors.initials: DI
authors.lastname: Fotiadis
mesh_terms: D000465:Algorithms; D001185:Artificial Intelligence; D055598:Chemical Phenomena; D008958:Models, Molecular; D015233:Models, Statistical; D019696:Peptidylprolyl Isomerase; D011392:Proline / Q000737:chemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D012372:ROC Curve; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013237:Stereoisomerism
chemical_list: D011506:Proteins; D011392:Proline; D019696:Peptidylprolyl Isomerase