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Effects of protein binding on a lipid bilayer containing local anesthetic articaine, and the potential of mean force calculation: a molecular dynamics simulation approach

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Abstract

Articaine, as a local anesthetic drug has been simulated in neutral and charged forms, and its interaction with the dimyristoylphosphatidylcholine (DMPC) lipid bilayer membrane is investigated by molecular dynamics simulation using GROMACS software. In order to obtain the optimum location of the drug molecules, as they penetrate into the membrane, umbrella sampling is applied and the free energy is calculated. The effect of protein binding to DMPC membrane on the process of drug diffusion through the membrane is considered. Five simulation systems are designed and by applying the potential of mean force, the molecular dynamics simulation on the system is performed. In light of the obtained results, the electrostatic potential, variation of lipid bilayer’s order parameter and the diffusion coefficient of drug are discussed.

Variations of Free energy versus the location of the drug molecule

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References

  1. Malamed SF, Gagnon S, Leblanc D (2000) Efficacy of articaine: a new amide local anesthetic. J Am Dent Assoc 131:635–642

    CAS  Google Scholar 

  2. Eeden SPV, Patel MF (2002) Prolonged paraesthesia following inferior alveolar nerve block using articaine. Br J Oral Maxillofac Surg 40:519–520

    Article  Google Scholar 

  3. Avdeef A, Box KJ, Comer JEA, Hibbert C, Tam KY (1998) pH-metric logP 10. Determination of liposomal membrane–water partition coefficients of ionizable drugs. Pharm Res 15:209–215

    Article  CAS  Google Scholar 

  4. Boulanger Y, Schreier S, Smith IC (1981) Molecular details of anesthetic–lipid interaction as seen by deuterium and phosphorus-31 nuclear magnetic resonance. Biochemistry 20:6824–6830

    Article  CAS  Google Scholar 

  5. Auger M, Smith IC, Mantsch HH, Wong PT (1990) High-pressure infrared study of phosphatidylserine bilayers and their interactions with the local anesthetic tetracaine. Biochemistry 29:2008–2015

    Article  CAS  Google Scholar 

  6. Ueda I, Yoshiba T (1999) Hydration of lipid membranes and the action mechanisms of anesthetics and alcohols. Chem Phys Lipids 101:65–79

    Article  CAS  Google Scholar 

  7. Mojumdar EH, Lyubartsev AP (2010) Molecular dynamics simulations of local anesthetic articaine in a lipid bilayer. J Biophysical Chemistry 153:27–35

    Article  CAS  Google Scholar 

  8. Song C, Lygre H, Nerdal W (2008) Articaine interaction with DSPC bilayer: a 13C and 31P solid-state NMR study. Eur J Pharm Sci 33:399–408

    Article  CAS  Google Scholar 

  9. Vree TB, Gielen MJM (2005) Clinical pharmacology and the use of articaine for local and regional anaesthesia. Best Pract Res Clin Anaesthesiol 19:293–308

    Article  CAS  Google Scholar 

  10. Tu K, Tarek M, Klein ML, Scharf D (1998) Effects of anesthetics on the structure of a phospholipid bilayer: molecular dynamics investigation of halothane in the hydrated liquid crystal phase of dipalmitoylphosphatidylcholine. Biophys J 75:2123–2134

    Article  CAS  Google Scholar 

  11. Castro V, Stevensson B, Dvinskikh SV, Högberg C-J, Lyubartsev AP, Zimmermann H, Sandström D, Maliniak A (2008) NMR investigations of interactions between anesthetics and lipid bilayers. Biochim Biophys Acta 1778:2604–2611

    Article  CAS  Google Scholar 

  12. Koubi L, Saiz L, Tarek M, Scharf D, Klein M (2003) Influence of anesthetic and nonimmobilizer molecules on the physical properties of a polyunsaturated lipid bilayer. J Phys Chem B 107:14500–14508

    Article  CAS  Google Scholar 

  13. Porasso RD, Bennett WFD, Oliveira-Costa SD, Cascales JJL (2009) Study of the benzocaine transfer from aqueous solution to the interior of a biological membrane. J Phys Chem B 113:9988–9994

    Article  CAS  Google Scholar 

  14. Högberg C-J, Maliniak A, Lyubartsev AP (2007) Dynamical and structural properties of charged and uncharged lidocaine in a lipid bilayer. Biophys Chem 125:416–424

    Article  Google Scholar 

  15. Högberg C-J, Lyubartsev AP (2008) Effect of local anesthetic lidocaine on electrostatic properties of a lipid bilayer. Biophys J 94:525–531

    Article  Google Scholar 

  16. Xiang T-X, Anderson BD (2006) Liposomal drug transport: a molecular perspective from molecular dynamics simulations in lipid bilayers. Adv Drug Deliv 58:1357–1378

    Article  CAS  Google Scholar 

  17. Eckenhoff RG (2001) Promiscuous ligands and attractive cavities: how do the inhaled anesthetics work. Mol Interv 1:258–268

    CAS  Google Scholar 

  18. Klauda JB, Brooks BR (2007) Sugar binding in lactose permease: anomeric state of a disaccharide influences binding structure. J Mol Biol 367:1523–1534

    Article  CAS  Google Scholar 

  19. Boudker O, Verdon G (2010) Structural perspectives on secondary active transporters. Trends Pharmacol Sci 31:418–426

    Article  CAS  Google Scholar 

  20. Boggara MB, Krishnamoorti R (2010) Partitioning of nonsterodial antiinflammatory drugs in lipid membranes: a molecular dynamics simulation study. Biophys J 98:586–595

    Article  CAS  Google Scholar 

  21. Yin Y, He X, Szewczyk P, Nguyen T, Chang G (2006) structure of the multidrug transporter EmrD from Escherichia coli. Science 312:741–744

    Article  CAS  Google Scholar 

  22. Papahadjoupoulos D, Jacobson K, Poste G, Shepherd G (1975) Effect of local anesthetics on membrane properties. I. Changes in the fluidity of phospholipid bilayer. Biochim Biophys Acta 394:504–519

    Article  Google Scholar 

  23. Lindahl E, Hess B, van der Spoel D (2001) GROMACS 3.0: a package for molecular simulation and trajectory analysis. J Mol Model 7:306–317

    CAS  Google Scholar 

  24. Van Der Spoel D, Lindahl E, Hess B, Groenhof G, Mark AE, Berendsen HJC (2005) GROMACS: Fast, flexible, and free. J Comput Chem 26:1701–1718

    Article  Google Scholar 

  25. Hess B, Kutzner C, Van der Spoel D, Lindahl E (2008) GROMACS4: algorithms for highly efficient, load-balanced, and scalable molecular simulation. J Chem Theory Comput 4:435–447

    Article  CAS  Google Scholar 

  26. Zheng H, Fang-di W, Wang B, Yan-xiang W (2011) Molecular dynamics simulation on the interfacial features of phenol extraction by TBP/dodecane in water. Comput Theor Chem 970:66–72

    Article  CAS  Google Scholar 

  27. Cafiso DS (1998) Dipole potentials and spontaneous curvature: membrane properties that could mediate anesthesia. Toxicol Lett 100–101:431–439

    Article  Google Scholar 

  28. Tieleman DP (2002) University of Calgary, Department of Biological Sciences. http://moose.bio.ucalgary.ca/index.php?Page=Structures_and_Topologies

  29. Berger O, Edholm O, Jähnig F (1997) Molecular dynamics simulations of a fluid bilayer of dipalmitoylphosphatidylcholine at full hydration, constant pressure and constant temperature. Biophys J 72:2002–2013

    Article  CAS  Google Scholar 

  30. Lindahl E, Edholm O (2000) Mesoscopic undulations and thickness fluctuations in lipid bilayers from molecular dynamics simulations. Biophys J 79:426–433

    Article  CAS  Google Scholar 

  31. Benz RW, Castro-Roman F, Tobias DJ, White SH (2005) Experimental validation of molecular dynamics simulations of lipid bilayers: a new approach. Biophys J 88:805–817

    Article  CAS  Google Scholar 

  32. Högberg C-J, Lyubartsev AP (2006) A molecular dynamics investigation of the influence of hydration and temperature on structural and dynamical properties of a dimyristoylphosphatidylcholine bilayer. J Phys Chem B 110:14326–14336

    Article  Google Scholar 

  33. Schuttelkopf AW, van Aalten DMF (2004) PRODRG: a tool for high-throughput crystallography of protein-ligand complexes. Acta Cryst 60:1355–1363

    Google Scholar 

  34. Hess B, Bekker H, Berendsen HJC, Fraaije J (1997) Lincs: a linear constraint solver for molecular simulations. J Comput Chem 18:1463–1472

    Article  CAS  Google Scholar 

  35. Hoover WG (1986) Constant–pressure equations of motion. Phys Rev A 34:2499–2500

    Article  Google Scholar 

  36. Parrinello M, Rahman A (1980) Crystal structure and pair potentials: a molecular dynamics study. Phys Rev Lett 45:1196–1199

    Article  CAS  Google Scholar 

  37. Essmann U, Perera L, Pedersen LG (1995) A smooth particle mesh Ewald method. J Chem Phys 103:8577–8593

    Article  CAS  Google Scholar 

  38. Kandt C, Ash WL, Tieleman DP (2007) Setting up and running molecular dynamics simulation of membrane proteins. Methods 41:475–488

    Article  CAS  Google Scholar 

  39. An Information Portal to Biological Macromolecular Structures, http://www.rcsb.org/

  40. Gromacs 4.5 Online Reference, http://manual.gromacs.org/

  41. Allen WJ, Lemkul JA, Bevan DR (2009) GridMat-MD: a grid-based membrane analysis tool for use with molecular dynamics. J Comput Chem 30(12):1952–1958. doi:10.1002/jcc.21172

    Article  CAS  Google Scholar 

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Acknowledgments

The authors express their thanks and gratitude to the High Performance Computing Research Center (HPCRC) of Amirkabir University of Technology (Tehran Polytechnic) for providing computer facilities.

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Authors and Affiliations

  1. Department of Chemistry, Amirkabir University of Technology, Tehran, Iran

    Sepideh Amjad-Iranagh

  2. Department of Chemical Engineering, Amirkabir University of Technology, Tehran, Iran

    Abbas Yousefpour & Hamid Modarress

  3. Department of Chemical Engineering, University of Kashan, Kashan, Iran

    Parto Haghighi

  4. 424 Hafez Ave, Tehran, Iran, 15875-4413

    Hamid Modarress

Authors
  1. Sepideh Amjad-Iranagh
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  2. Abbas Yousefpour
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  3. Parto Haghighi
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  4. Hamid Modarress
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Correspondence to Hamid Modarress.

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Amjad-Iranagh, S., Yousefpour, A., Haghighi, P. et al. Effects of protein binding on a lipid bilayer containing local anesthetic articaine, and the potential of mean force calculation: a molecular dynamics simulation approach. J Mol Model 19, 3831–3842 (2013). https://doi.org/10.1007/s00894-013-1917-6

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  • DOI: https://doi.org/10.1007/s00894-013-1917-6

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