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In silico predictions of 3D structures of linear and cyclic peptides with natural and non‐proteinogenic residues
Author(s) -
Beaufays Jérôme,
Lins Laurence,
Thomas Annick,
Brasseur Robert
Publication year - 2012
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.1410
Subject(s) - in silico , cyclic peptide , peptide , threading (protein sequence) , chemistry , amino acid , homology modeling , protein structure , stereochemistry , biochemistry , enzyme , gene
We extended the use of Peplook, an in silico procedure for the prediction of three‐dimensional (3D) models of linear peptides to the prediction of 3D models of cyclic peptides and thanks to the ab initio calculation procedure, to the calculation of peptides with non‐proteinogenic amino acids. Indeed, such peptides cannot be predicted by homology or threading. We compare the calculated models with NMR and X‐ray models and for the cyclic peptides, with models predicted by other in silico procedures (Pep‐Fold and I‐Tasser). For cyclic peptides, on a set of 38 peptides, average root mean square deviation of backbone atoms (BB‐RMSD) was 3.8 and 4.1 Å for Peplook and Pep‐Fold, respectively. The best results are obtained with I‐Tasser (2.5 Å) although evaluations were biased by the fact that the resolved Protein Data Bank models could be used as template by the server. Peplook and Pep‐Fold give similar results, better for short (up to 20 residues) than for longer peptides. For peptides with non‐proteinogenic residues, performances of Peplook are sound with an average BB‐RMSD of 3.6 Å for ‘non‐natural peptides’ and 3.4 Å for peptides combining non‐proteinogenic residues and cyclic structure. These results open interesting possibilities for the design of peptidic drugs. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.