Abstract
BackgroundIn peptides and proteins, only a small percentile of peptide bonds adopts the cis configuration. Especially in the case of amide peptide bonds, the amount of cis conformations is quite limited thus hampering systematic studies, until recently. However, lately the emerging population of databases with more 3D structures of proteins has produced a considerable number of sequences containing non-proline cis formations (cis-nonPro).ResultsIn our work, we extract regular expression-type patterns that are descriptive of regions surrounding the cis-nonPro formations. For this purpose, three types of pattern discovery are performed: i) exact pattern discovery, ii) pattern discovery using a chemical equivalency set, and iii) pattern discovery using a structural equivalency set. Afterwards, using each pattern as predicate, we search the Eukaryotic Linear Motif (ELM) resource to identify potential functional implications of regions with cis-nonPro peptide bonds. The patterns extracted from each type of pattern discovery are further employed, in order to formulate a pattern-based classifier, which is used to discriminate between cis-nonPro and trans-nonPro formations.ConclusionsIn terms of functional implications, we observe a significant association of cis-nonPro peptide bonds towards ligand/binding functionalities. As for the pattern-based classification scheme, the highest results were obtained using the structural equivalency set, which yielded 70% accuracy, 77% sensitivity and 63% specificity.
Highlights
In peptides and proteins, only a small percentile of peptide bonds adopts the cis configuration
Cis peptide bonds are further distributed in two categories, according to the residues they connect; namely, imide bonds which occur between any amino acid and proline, and amide bonds which bind any amino acid and any amino acid except proline, out of which 5.2% and 0.03% are in cis conformation, respectively
Nuclear Magnetic Resonance (NMR) experiments on oligopeptides have proven that the peptide bond between two amino acids is influenced by the sequence which spans the proximity of the bond [4]
Summary
Only a small percentile of peptide bonds adopts the cis configuration. Nuclear Magnetic Resonance (NMR) experiments on oligopeptides have proven that the peptide bond between two amino acids is influenced by the sequence which spans the proximity of the bond [4]. This is in accordance with several methods aiming to predict the peptide bond conformation using only the amino acid sequence, or sequence-extracted features [5,6,7,8,9]. The identification of the peptide bond conformation solely from the primary amino acid sequence is of great importance, the black-box architecture of these methods does not provide adequate (if not any) justification about the respective predictions; limited biological insight can be deduced. Towards the exploration of similar sequence-driven characteristics of the protein structure (e.g. protein disorder [11] and secondary structure formations [12,13]) or even for proline cis peptide bonds [14], pattern-based methodologies have been proven quite beneficial
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