The discovery of a new class of cell-penetrating peptides (CPPs) two decade ago rapidly changed the general view on the inability of highly polar and charged molecules to enter cells without causing irreversible membrane damage. Since then the astonishing ability of CPPs to penetrate almost any cell has been exploited to deliver various biomolecules into cells and tissues. However, mechanisms of the energy-independent direct membrane crossing by structurally diverse CPPs still remains a mystery.
Here we provide a web-based tool CPPpred aimed at validation of ability of peptides to penetrate across membranes via membrane deformation. This tool implements novel computational methods based on physically realistic description of different aspects of membrane-peptide interactions, including peptide insertion into membranes, formations of α-helices or β-stands/sheets, and peptide-induced membrane thinning, curvature changes, or formation of pores and vesicles. This would help to understand mechanisms of direct peptide translocation across natural and artificial membranes. CPPpred is a general tool for discovery, analysis, design, and optimization of CPPs and other membrane-active peptides and proteins.
Lomize M.A., Pogozheva I,D, Joo H., Mosberg H.I., Lomize A.L.: OPM database and PPM web server: resources for positioning of proteins in membranes. Nucleic Acids Res., 2012, 40 (Database issue):D370-376 [PubMed]