Reference : "De novo" design of peptides with specific lipid-binding properties
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
"De novo" design of peptides with specific lipid-binding properties
Lins, Laurence mailto [Université de Liège - ULiège > > Gembloux Agro-Bio Tech >]
Charloteaux, Benoît [Université de Liège - ULiège > > Gembloux Agro-Bio Tech >]
Heinen, C. [Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Histologie humaine >]
Thomas, Annick [Université de Liège - ULiège > Chimie et bio-industries > Centre de Bio. Fond. - Section de Biologie moléc. et numér. >]
Brasseur, Robert mailto [Université de Liège - ULiège > > Gembloux Agro-Bio Tech >]
Biophysical Journal
Biophysical Society
Yes (verified by ORBi)
[en] In this study, we describe an in silico method to design peptides that can be made of non-natural amino acids and elicit specific membrane-interacting properties. The originality of the method holds in the capacities developed to design peptides from any non-natural amino acids as easily as from natural ones, and to test the structure stability by an angular dynamics rather than the currently-used molecular dynamics. The goal of this study was to design a non-natural tilted peptide. Tilted peptides are short protein fragments able to destabilize lipid membranes and characterized by an asymmetric distribution of hydrophobic residues along their helix structure axis. The method is based on the random generation of peptides and their election on three main criteria: mean
hydrophobicity and the presence of at least one polar residue; tilted insertion at the level of the acyl chains of lipids of a membrane; and conformational stability in that hydrophobic phase. From 10,000,000 randomly-generated peptides, four met all the criteria. One was synthesized and tested for its lipid-destabilizing properties. Biophysical assays showed that the "de novo"
peptide made of non-natural amino acids is helical either in solution or intolipids as tested by Fourier transform infrared spectroscopy and is able to induce liposome fusion. These results are in agreement with the calculations andvalidate the theoretical approach.
Researchers ; Professionals

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