In silico predictions of 3D structures of linear and cyclic peptides with natural and non-proteinogenic residues.
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.
Centre de Biophysique Moléculaire Numérique, ULg, Gembloux Agro Bio Tech, Passage des Déportés, 2, 5030, Gembloux, Belgium.
Jérôme
J
Beaufays
Laurence
L
Lins
Annick
A
Thomas
Robert
R
Brasseur
D000465:Algorithms; D000595:Amino Acid Sequence; D003198:Computer Simulation; D015195:Drug Design; D055808:Drug Discovery; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012984:Software
D010456:Peptides, Cyclic