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Coarse Grain Molecular Dynamics Simulation of Drug Carrier Translocation into Cell Membrane

Damirchi, Behzad | 2014

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  1. Type of Document: M.Sc. Thesis
  2. Language: Farsi
  3. Document No: 45421 (08)
  4. University: Sharif University of Technology
  5. Department: Mechanical Engineering
  6. Advisor(s): Saidi, Mohammad Said; Firoozabadi, Bahar
  7. Abstract:
  8. With the increasing development of the pharmaceutical industry and producing drugs with specific performance, its transfer into cells is also very important. Cell membranes are effectively impermeable to hydrophilic compounds unless the permeation is facilitated by dedicated transport systems. This means that many hydrophilic compounds, including many promising drug candidates, fail to reach their intracellular target because they cannot spontaneously cross lipid membranes. As a consequence, there is much interest in finding ways to facilitate the transport of molecules across cell membranes. Cell-penetrating peptides (CPPs) in particular have shown much promise as potential delivery agents that have been claimed to penetrate cell membranes in an energy- and receptor-independent manner.
    In the present investigation, the translocation of PENETRATIN into the cell membrane is carried out applying constant velocity steered molecular dynamics via MARTINI coarse grain approach. Energy barrier upon the insertion is calculated and its diffusion in the membrane is considered. It is shown that pore formation phenomenon breaks down the energy barrier and facilitates the translocation process which is in agreement with previous researches.
    In order to consider a challenging problem, HDL stability problem which is known as good cholesterol, is investigated. Comparing the results between our simulation and previous studies reveals a good agreement and validates our simulation. Finally, several lipid protein ratios are applied on HDL structure which revealed novel structural modes of this blood component
  9. Keywords:
  10. Steered Molecular Dynamics ; Drug Delivery ; Coarse Grain Molecular Dynamic ; Energy Barrier Calculation ; Cell Penetrating Peptide (CPP) ; High Density Lipoprotein (HDL)

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