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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.

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This paper deals with atomistic modeling of nanomechanical behavior of actin monomer. The major cytoskeletal protein of most cells is actin, which is responsible for the mechanical properties of the cells. Actin also plays critical mechanical roles in many cellular processes which gives structural support to cells and links the interior of the cell with its surroundings. Based on the accuracy of atomistic-based methods such as molecular dynamics simulations, in this paper, we perform a series of steered molecular dynamics simulations on both ATP and ADP single actin monomers to determine their intrinsic molecular strength. The effect of virtual spring of steered molecular dynamics on the mechanical behavior of actin monomer is investigated. The results reveal increasing the virtual spring constant leads to convergence of the stiffness. The stiffness of ADP actin and ATP actin calculated as 215.16 and 228.24 pN/Å, respectively. The results also show higher stiffness and Young’s modulus for ATP G-actin in comparison to ADP G-actin. In order to compare the behavior of ATP and ADP G-actins, the number of hydrogen bonds and nonbonded energies between the nucleotide and the protein is analyzed. The obtained persistent length is 15.61 µm which is in good agreement with the other reported literature values.

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In this study, we tried to have investigation of elastic properties of Prefoldin nano-actuator on the microscopic scale. Prefoldin is a molecular chaperone that prevented the aggregation of misfolded proteins and it has been shown that it can also serve as a Nano-actuator (drug delivery). To this end, steered molecular dynamics simulations have been used, which investigate the theory of spring constant in the molecular test based on the theory of two springs in series. The results expressed in form of young’s modulus. The results show that Prefoldin nano actuator exhibit different behaviors at different pulling rates and to what extent of tension, each tentacle of this nano actuator remains stable. The resulting Young's modulus for the Prefoldin chains was obtained at a rate of (3-3.3 ± 0.01 Gpa). By providing the complete understanding of mechanical properties of Prefoldin nano actuator, it is possible to exact investigating of Prefoldin nano actuator applications in intelligent drug delivery and capture the pathogenic cargos.