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Molecular dynamics simulations and free energy profile of Paracetamol in DPPC and DMPC lipid bilayers

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Abstract

Molecular dynamics (MD) simulations and biased MD simulation were carried out for the neutral form of Paracetamol inserted in fully hydrated dipalmitoylphosphatidylcholine (DPPC) and dimyristoylphosphatidylcholine (DMPC) lipid bilayers. For comparison, fully hydrated DMPC and DPPC lipid bilayers were also simulated separately without Paracetamol. The simulation time for each system was 50 ns. At two concentrations of Paracetamol, various properties of the lipid bilayer such as area per lipid, order parameter, diffusion coefficient, radial distribution function, electrostatic potential, mass density and hydrogen bonds have been calculated. Also, the convergence in time of the free energy profile of the Paracetamol along a DPPC bilayer normal was calculated by umbrella sampling method. From the obtained results, it can be concluded that neutral form of Paracetamol shows a generally similar behaviour in DPPC and DMPC lipid bilayers. It was shown that the addition of Paracetamol causes a decrease in tail order parameter of both DPPC and DMPC lipid bilayers and the tail of Paracetamol adopts an inward orientation in the lipid bilayers. Also from the free energy profile, the high penetration barrier in the bilayer centre was determined.

The behaviour of Paracetamol in different dosages in two types of lipid bilayer membranes, DPPC and DMPC has been investigated by MD simulation. For the neutral form of the drug, the best position in the membrane has been identified by free energy calculations.

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Acknowledgments

We thank the High Performance Computing Research Center (HPCRC) of Amirkabir University of Technology (Tehran Polytechnic) for provision of computer facilities.

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Authors and Affiliations

  1. Department of Chemical Engineering, Amirkabir University of Technology, 15875-4413, Tehran, Iran

    YOUSEF NADEMI, ABBAS YOUSEFPOUR, SEYEDEH ZAHRA MOUSAVI & HAMID MODARRESS

  2. Department of Chemistry, Amirkabir University of Technology, 15875-4413, Tehran, Iran

    SEPIDEH AMJAD IRANAGH

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  1. YOUSEF NADEMI
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Correspondence to HAMID MODARRESS.

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Supplementary information

The supplementary information figures S1–S4 and table S1 can be seen in www.ias.ac.in/chemsci website.

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12039_2013_556_Fig1_ESM.tif

Mass density of different components for DMPC lipid bilayer systems: 4 Neutral Paracetamol system (⎕), 8 Neutral Paracetamol system (+), DMPC reference system (☆), DMPC system containing 4 Paracetamol (⎕), DMPC system containing 8 Paracetamol (⎕ · ⎕), water (♢). (DOC 870 KB)

The angular distribution of the paracetamol long axis in DMPC lipid bilayer. (DOC 1.4 MB)

Average number of different hydrogen bonds for paracetamol in simulated systems. (DOC 62.5 KB)

Lateral mean square displacement of paracetamol in DMPC lipid bilayers. (DOC 284 KB)

DMPC membrane electrostatic potential. (DOC 2.46 MB)

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NADEMI, Y., AMJAD IRANAGH, S., YOUSEFPOUR, A. et al. Molecular dynamics simulations and free energy profile of Paracetamol in DPPC and DMPC lipid bilayers. J Chem Sci 126, 637–647 (2014). https://doi.org/10.1007/s12039-013-0556-x

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  • DOI: https://doi.org/10.1007/s12039-013-0556-x

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