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Modeling of non-covalent complexes of the cell-penetrating peptide CADY and its siRNA cargo
Crowet, Jean-Marc; Lins, Laurence; Deshayes, Sébastien et al.
2013In European Biophysics Journal, 42 (S1), p. 63
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Abstract :
[en] CADY is a cell-penetrating peptide spontaneously making non-covalent complexes with short interfering RNAs (siRNAs) in water. Neither the structure of CADY nor that of the complexes is resolved. We have calculated and analyzed 3D models of CADY and of the non-covalent CADY–siRNA complexes in order to understand their formation and stabilization. Data from the ab initio calculations and molecular dynamics support that, in agreement with the experimental data, CADY is a polymorphic peptide partly helical. We calculated and compared several complexes with peptide/siRNA ratios of up to 40. The initial binding of CADYs is essentially due to the electrostatic interactions of the arginines with siRNA phosphates. Due to a repetitive arginine motif (XLWR(K)), CADYs can adopt multiple positions at the siRNA surface. Nevertheless, several complex properties are common: an average of 14 ± 1 CADYs is required to saturate a siRNA. The 40 CADYs/siRNA that is the optimal ratio for vector stability always corresponds to two layers of CADYs per siRNA and the peptide cage is stabilized by hydrophobic CADY–CADY contacts. The analysis demonstrates that the hydrophobicity, the positive charges and the polymorphism of CADY are mandatory to make stable the CADY–siRNA complexes.
Research center :
Centre de Biophysique Moléculaire Numérique
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Crowet, Jean-Marc ;  Université de Liège - ULiège > Chimie et bio-industries > Biophysique moléc. numér.
Lins, Laurence  ;  Université de Liège - ULiège > Chimie et bio-industries > Biophysique moléc. numér.
Deshayes, Sébastien
Divita, Gilles
Morris, May
Brasseur, Robert ;  Université de Liège - ULiège > Chimie et bio-industries > Biophysique moléc. numér.
Thomas, Annick
Language :
English
Title :
Modeling of non-covalent complexes of the cell-penetrating peptide CADY and its siRNA cargo
Publication date :
2013
Event name :
9th European Biophysics Congress
Event organizer :
The Portuguese Biophysical Society
Event place :
Lisbon, Portugal
Event date :
du 13 au 17 Juillet
Audience :
International
Journal title :
European Biophysics Journal
ISSN :
0175-7571
eISSN :
1432-1017
Publisher :
Springer Verlag, Berlin, Germany
Special issue title :
9th European Biophysics Congress
Volume :
42
Issue :
S1
Pages :
63
Peer reviewed :
Peer Reviewed verified by ORBi
Name of the research project :
IAP/Belspo P7/44 project : Integrative Protein Science (iPROS)
Funders :
BELSPO - SPP Politique scientifique - Service Public Fédéral de Programmation Politique scientifique
Available on ORBi :
since 10 December 2013

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