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Dynamics of heroin molecule inside the lipid membrane: a molecular dynamics study

  • Satnam SinghEmail author
Original Paper
  • 160 Downloads

Abstract

Heroin, or diamorphine (C21H23NO5), is an opium product used for various pharmaceutical and euphoric purposes. In this work, the molecular dynamics simulation study of the heroin inside the two lipid bilayers, dipalmitoylphosphatidylcholine (DMPC) and dipalmitoylphosphatidylcholine (DPPC) are presented. The whole study was conducted at three different temperatures. The location of the heroin drug, the nature of the diffusion, rotational correlation function and structural variation inside both lipid bilayers is studied. Moreover, the free energy of the solvation of the drug inside both lipid bilayers is calculated. It is found that during the whole molecular dynamics study, the drug locates at the center of both lipid membranes. The effect of the temperature is not seen at the drug location. The nature of the diffusion of the heroin drug is anomalous. The radius of gyration is calculated to study the structural variations of the heroin molecule inside both lipid bilayers. It is found that the heroin molecule does not change its structure at three temperatures. From the rotational correlation function, it is seen that the drug is more hindered for rotation inside the DPPC lipid bilayer as compared to the DMPC lipid bilayer. It is applicable for all three temperatures. The rotational correlation time of the drug is decreased while the temperature of the system is increased. In the case of DMPC, there is an abrupt change in rotational correlation time while the phase is changed.

Keywords

Heroin Drug Opium 

Notes

Acknowledgments

All simulations were performed on an Intel Core i5 processors. Whole data was plotted by GNU plot [37]. For visualization, the molecules Avogadro, Chimera [38], and VMD [39] were used.

References

  1. 1.
    Kennedy AP, Epstein DH, Jobes ML, Agage D, Tyburski M, Phillips KA, Ali AA, Bari R, Hossain SM, Hovsepian K, Rahman MM, Ertin E, Kumar S, Preston KL (2015) Continuous in-the-field measurement of heart rate Correlates of drug use, craving, stress, and mood in polydrug users. Drug Alcohol Depend. 151:159–166CrossRefGoogle Scholar
  2. 2.
    Darke S, Duflou J (2016) The toxicology of heroin-related death: estimating survival times. Addiction 111(9):1607–1613CrossRefGoogle Scholar
  3. 3.
    Strang J, Groshkova T, Uchtenhagen A, van den Brink W, Haasen C, Schechter MT, Lintzeris N, Bell J, Pirona A, Oviedo-Joekes E et al (2015) And heroin on trial: systematic review and meta-analysis of randomised trials of diamorphine-prescribing as treatment for refractory heroin addiction. Br J Psychiatr 207 (1):5–14CrossRefGoogle Scholar
  4. 4.
    Sharma A, Govindan P, Toukatly M, Healy J, Henry C, Senter S, Najafian B, Kestenbaum B (2018) Heroin use is associated with aa-type kidney amyloidosis in the pacific northwest. Clinical Journal of the American Society of Nephrology 13:CJN–13641217Google Scholar
  5. 5.
    Piepenbrink MS, Samuel M, Zheng B, Carter B, Fucile C, Bunce C, Kiebala M, Khan AA, Thakar J, Maggirwar SB, Morse D, Rosenberg AF, Haughey NJ, Valenti W, Keefer MC, Kobie JJ (2016) Humoral dysregulation associated with increased systemic inflammation among injection heroin users. PLOS ONE 11:1–21, 07CrossRefGoogle Scholar
  6. 6.
    Safarinejad MR, Asgari SA, Farshi A, Ghaedi G, Kolahi AA, Iravani S, Khoshdel AR (2013) The effects of opiate consumption on serum reproductive hormone levels, sperm parameters, seminal plasma antioxidant capacity and sperm DNA integrity. Reprod Toxicol 36:18–23CrossRefGoogle Scholar
  7. 7.
    Pattison LP, McIntosh S, Budygin EA, Hemby SE (2012) Differential regulation of accumbal dopamine transmission in rats following cocaine, heroin and speedball self-administration. J Neurochem 122(1):138–146CrossRefGoogle Scholar
  8. 8.
    Solis E, Cameron-Burr KT, Shaham Y, Kiyatkin EA (2017) Intravenous heroin induces rapid brain hypoxia and hyperglycemia that precede brain metabolic response. eNeuroGoogle Scholar
  9. 9.
    Bond C, LaForge KS, Tian M, Melia D, Zhang S, Borg L, Gong J, Schluger J, Strong JA, Leal SM, Tischfield JA, Kreek MJ, Yu L (1998) Single-nucleotide polymorphism in the human mu opioid receptor gene alters β-endorphin binding and activity. Possible implications for opiate addiction. Proc Natl Acad Sci 95(16):9608–9613CrossRefGoogle Scholar
  10. 10.
    Veilleux JC, Colvin PJ, Anderson J, York C, Heinz AJ (2010) A review of opioid dependence treatment. Pharmacological and psychosocial interventions to treat opioid addiction. Clin Psychol Rev 30(2):155–166CrossRefGoogle Scholar
  11. 11.
    Kumar S, Yadav DK, Choi E, Kim M (2018) Insight from molecular dynamic simulation of reactive oxygen species in oxidized skin membrane. Sci Rep 8(1):13271CrossRefGoogle Scholar
  12. 12.
    Yadav DK, Kumar S, Choi E, Sharma P, Misra S, Kim M (2018) Insight into the molecular dynamic simulation studies of reactive oxygen species in native skin membrane. Front Pharmacol., 9Google Scholar
  13. 13.
    Johnson SJ, Bayerl TM, McDermott DC, Adam GW, Rennie AR, Thomas RK, Sackmann E Structure of an adsorbed dimyristoylphosphatidylcholine bilayer measured with specular reflection of neutronsGoogle Scholar
  14. 14.
    Kargar F, Emadi S, Fazli H (2017) The molecular behavior of a single β-amyloid inside a dipalmitoylphosphatidylcholine bilayer at three different temperatures: an atomistic simulation study: Aβ interaction with DPPC: atomistic simulation. Proteins: Struct Funct Bioinf 85(7):1298–1310CrossRefGoogle Scholar
  15. 15.
    Yadav DK, Kumar S, Misra S, Yadav L, Teli M, Sharma P, Chaudhary S, Kumar N , Choi EH, Kim HS, Kim MH (2018) Molecular insights into the interaction of rons and thieno [3, 2-c] pyran analogs with SIRT6/COX-2: a molecular dynamics study. Sci Rep 8(1):4777CrossRefGoogle Scholar
  16. 16.
    Van Der Spoel D, Lindahl E, Hess B, Groenhof G, Mark AE, Berendsen HJ, David VDS, Erik L, Berk H, Gerrit G, Alan ME, Herman BJC (2005) Gromacs: fast, flexible, and free. J Comput Chem 26(16):1701–1718CrossRefGoogle Scholar
  17. 17.
    Hess B, Kutzner C, Spoel DVD, Lindahl E (2008) Gromacs 4: Algorithms for highly efficient load-balanced and scalable molecular simulation. J Chem Theory Comput 4(3):435– 447CrossRefGoogle Scholar
  18. 18.
    Oostenbrink C, Villa A, Mark AE, Gunsteren WFV (2004) A biomolecular force field based on the free enthalpy of hydration and solvation: the GROMOS force-field parameter sets 53a5 and 53a6. J Comput Chem 25 (13):1656–1676CrossRefGoogle Scholar
  19. 19.
    Poger D, Gunsteren V, Wilfred F, Mark AE (2010) A new force field for simulating phosphatidylcholine bilayers. J Comput Chem 31(6):1117–1125CrossRefGoogle Scholar
  20. 20.
    Malde AK, Zuo L, Breeze M, Stroet M, Poger D, Nair PC, Oostenbrink C, Mark AE (2011) An automated force field topology builder (ATB) and repository: version 1.0. J Chem Theory Comput 7 (12):4026–4037CrossRefGoogle Scholar
  21. 21.
    Berendsen HJ, van der Spoel D, van Drunen R (1995) GROMACS: a message-passing parallel molecular dynamics implementation. Comput Phys Commun 91(1-3):43–56CrossRefGoogle Scholar
  22. 22.
    Lindahl E, Hess B, Spoel DVD (2001) Gromacs 3.0: a package for molecular simulation and trajectory analysis. J Mol Model 7(8):306–317CrossRefGoogle Scholar
  23. 23.
    Páll S., Hess B (2013) A flexible algorithm for calculating pair interactions on {SIMD} architectures. Comput Phys Commun 184(12):2641–2650CrossRefGoogle Scholar
  24. 24.
    Wennberg CL, Murtola T, Hess B, Lindahl E (2013) Lennard–Jones lattice summation in bilayer simulations has critical effects on surface tension and lipid properties. J Chem Theory Comput 9(8):3527–3537CrossRefGoogle Scholar
  25. 25.
    Wennberg CL, Murtola T, Páll S., Abraham MJ, Hess B, Lindahl E (2015) Direct-space corrections enable fast and accurate Lorentz–Berthelot combination rule Lennard–Jones lattice summation. J Chem Theory Comput 11(12):5737–5746CrossRefGoogle Scholar
  26. 26.
    Essmann U, Perera L, Berkowitz ML, Darden T, Lee H, Pedersen LG (1995) A smooth particle mesh Ewald method. J Chem Phys 103:8577–8593CrossRefGoogle Scholar
  27. 27.
    Darden T, York D, Pedersen L (1993) Particle mesh Ewald: an n log (n) method for Ewald sums in large systems. J Chem Phys 98(12):10089–10092CrossRefGoogle Scholar
  28. 28.
    Berger O, Edholm O, Jahnig F (2002) Molecular dynamics simulations of a fluid bilayer of dipalmitoylphosphatidylcholine at full hydration, constant pressure, and constant temperature. Biophys J 72(5):1997Google Scholar
  29. 29.
    Evans DJ, Holian BL (1985) The Nose-Hoover thermostat. J Chem Phys 83(8):4069–4074CrossRefGoogle Scholar
  30. 30.
    Parrinello M, Rahman A (1981) Polymorphic transitions in single crystals: a new molecular dynamics method. J Appl Phys 52(12):7182–7190CrossRefGoogle Scholar
  31. 31.
    Hess B, Bekker H, Berendsen H, Fraaije JGEM, et al (1997) Lincs: a linear constraint solver for molecular simulations. J Comput Chem 18(12):1463–1472CrossRefGoogle Scholar
  32. 32.
    Jorge M, Garrido NM, Queimada AJ, Economou IG, Macedo EA (2010) Effect of the integration method on the accuracy and computational efficiency of free energy calculations using thermodynamic integration. J Chem Theory Comput 6(4):1018–1027CrossRefGoogle Scholar
  33. 33.
    Javanainen M, Hammaren H, Monticelli L, Jeon J, Miettinen MS, Martinez-Seara H, Metzler R, Vattulainen I (2013) Anomalous and normal diffusion of proteins and lipids in crowded lipid membranes. Faraday Discuss 161:397–417CrossRefGoogle Scholar
  34. 34.
    Zhang R, Duan X, Ding M, Shi T (2018) Molecular dynamics simulation of salt diffusion in polyelectrolyte assemblies. The Journal of Physical Chemistry B 122:6656–6665CrossRefGoogle Scholar
  35. 35.
    Feng S, Voth GA (2010) Molecular dynamics simulations of imidazolium-based ionic liquid/water mixtures. Alkyl side chain length and anion effects. Fluid Phase Equilib 294(1):148–156CrossRefGoogle Scholar
  36. 36.
    (2011) Gromacs 4.5.4 Manual: http://www.gromacs.org/Documentation/Manual
  37. 37.
    Williams T, Kelley C, et al (2013) Gnuplot 4.6: an interactive plotting program, http://gnuplot.sourceforge.net/
  38. 38.
    Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE (2004) UCSF Chimera—a visualization system for exploratory research and analysis. J Comput Chem 25(13):1605–1612CrossRefGoogle Scholar
  39. 39.
    Humphrey W, Dalke A, Schulten K (1996) Vmd: visual molecular dynamics. J Mol Graph Model 14(1):33–38CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Physical SciencesIndian Institute of Science Education & Research (IISER) MohaliPunjabIndia

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