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Cell penetrating peptides: Modelling transmembrane insertion

Objective

The lipid bilayers of biological membranes are not permeable for hydrophilic molecules under physiological conditions. However, numerous biomedical applications, such as drug delivery and gene therapy, rely on reliable way of the transmembrane translocatio n of proteins, fragments of DNA and other water-soluble compounds. Thus, the search for possible transduction agents continued for several decades. Cell-penetrating peptides (CPPs) are recognized to be amino acid sequences, which make an effective transduction of the hydrophilic molecules through the cell membrane possible.

The transduction is claimed to be spontaneous and energy-independent process. This makes CPPs very attractive for numerous applications. Some of the CPPs are structural parts of natural proteins, while others are purely artificial or engineered sequences. Different molecular cargoes can cross the membrane being covalently bound to CPPs, which is already used in biomedical researches. Although the CPPs are widely studied for more then a decade, their transduction mechanism is still not understood. Several possible models are proposed, however, there are no experimental techniques, which can reveal the molecular details of the translocation process and distinguish between these models.

The macroscopic transduction rates of particular CPPs are of great interest for practical applications, but cannot be easily determined experimentally. Molecular dynamics simulations provide unique opportunity to study the transduction of CPPs in atomic details and to measure the transduction rates in any desirable conditions. In the present project extensive molecular dynamics simulations of various lipid bilayers in the presence of the cell penetrating peptides will be conducted in order to observe the events of transduction and characterize this process in full molecular details. Transduction rates will be calculated combining the results of MD simulations with theoretical approaches.

Field of science

  • /natural sciences/chemical sciences/organic chemistry/amines
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins
  • /medical and health sciences/medical biotechnology/genetic engineering/gene therapy
  • /natural sciences/biological sciences/biochemistry/biomolecules/lipids

Call for proposal

FP6-2005-MOBILITY-7
See other projects for this call

Funding Scheme

IIF - Marie Curie actions-Incoming International Fellowships

Coordinator

RIJKSUNIVERSITEIT GRONINGEN
Address
Oude Boteringestraat 44
Groningen
Netherlands