Coarse grain molecular dynamics simulation of drug carrier penetration into cell membrane

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. 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. In order to study the orientation of peptide as it get closer to the membrane, equilibrium simulation is carried out and it is shown that to investigate the penetration process, we need to apply steered molecular dynamics simulation. 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. Furthermore, 110 kJ/mol energy barrier is obtained from simulations for this peptide.