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Study of procaine and tetracaine in the lipid bilayer using molecular dynamics simulation

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Abstract

Despite available experimental results, the molecular mechanism of action of local anesthetics upon the nervous system and contribution of the cell membrane to the process are still controversial. In this work, molecular dynamics simulations were performed to investigate the effect of two clinically used local anesthetics, procaine and tetracaine, on the structure and dynamics of a fully hydrated dimyristoylphosphatidylcholine lipid bilayer. We focused on comparing the main effects of uncharged and charged drugs on various properties of the lipid membrane: mass density distribution, diffusion coefficient, order parameter, radial distribution function, hydrogen bonding, electrostatic potential, headgroup angle, and water dipole orientation. To compare the diffusive nature of anesthetic through the lipid membrane quantitatively, we investigated the hexadecane/water partition coefficient using expanded ensemble simulation. We predicted the permeability coefficient of anesthetics in the following order: uncharged tetracaine > uncharged procaine > charged tetracaine > charged procaine. We also shown that the charged forms of drugs are more potent in hydrogen bonding, disturbing the lipid headgroups, changing the orientation of water dipoles, and increasing the headgroup electrostatic potential more than uncharged drugs, while the uncharged drugs make the lipid diffusion faster and increase the tail order parameter. The results of these simulation studies suggest that the different forms of anesthetics induce different structural modifications in the lipid bilayer, which provides new insights into their molecular mechanism.

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References

  • Almeida PFF, Vaz WLC, Thompson TE (1992) Lateral diffusion in the liquid phases of dimyristoylphosphatidylcholine/cholesterol lipid bilayers: a free volume analysis. Biochemistry 31:6739–6747

    Article  CAS  PubMed  Google Scholar 

  • Auger M, Smith ICP, Jarrell HC (1989) Interactions of the local anesthetic tetracaine with glyceroglycolipid bilayers: a 2H-NMR study. Biochim Biophys Acta (BBA)-Biomembr 981:351–357

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Awoonor-Williams E, Rowley CN (2016) Molecular simulation of nonfacilitated membrane permeation. Biochim Biophys Acta (BBA)-Biomembr 1858:1672–1687

    Article  CAS  Google Scholar 

  • Becker DE, Reed KL (2006) Essentials of local anesthetic pharmacology. Anesth Prog 53:98–109

    Article  PubMed  PubMed Central  Google Scholar 

  • Becker DE, Reed KL (2012) Local anesthetics: review of pharmacological considerations. Anesth Prog 59:90–102

    Article  PubMed  PubMed Central  Google Scholar 

  • Bemporad D, Luttmann C, Essex JW (2005) Behaviour of small solutes and large drugs in a lipid bilayer from computer simulations. Biochim Biophys Acta (BBA)-Biomembr 1718:1–21

    Article  CAS  Google Scholar 

  • Berendsen HJC, Postma JPM, van Gunsteren WF, Hermans J (1981) Interaction models for water in relation to protein hydration. Intermolecular forces. Springer, New York, pp 331–342

    Chapter  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Broemstrup T, Reuter N (2010) Molecular dynamics simulations of mixed acidic/zwitterionic phospholipid bilayers. Biophys J 99:825–833

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Buchwald P, Bodor N (1998) Octanol-water partition: searching for predictive models. Curr Med Chem 5:353–380

    CAS  PubMed  Google Scholar 

  • Butterworth J, Strichartz GR (1990) Molecular mechanisms of local anesthesia: a review. Anesthesiology 72:711–734

    Article  CAS  PubMed  Google Scholar 

  • Cabeca LF, Pickholz M, de Paula E, Marsaioli AJ (2009) Liposome–prilocaine interaction mapping evaluated through STD NMR and molecular dynamics simulations. J Phys Chem B 113:2365–2370

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Cantor RS (1997) The lateral pressure profile in membranes: a physical mechanism of general anesthesia. Biochemistry 36:2339–2344

    Article  CAS  PubMed  Google Scholar 

  • Cantor RS (1999) Lipid composition and the lateral pressure profile in bilayers. Biophys J 76:2625–2639

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cascales JJL, Cifre JGH, de la Torre JG (1998) Anaesthetic mechanism on a model biological membrane: a molecular dynamics simulation study. J Phys Chem B 102:625–631

    Article  Google Scholar 

  • Catterall W, Mackie K (1996) Local anesthetics. Goodman Gilman’s Pharmacol basis Ther, 9th edn. McGraw Hill, New York, pp 331–347

    Google Scholar 

  • Chiu SW, Pandit SA, Scott HL, Jakobsson E (2009) An improved united atom force field for simulation of mixed lipid bilayers. J Phys Chem B 113:2748–2763

    Article  CAS  PubMed  Google Scholar 

  • Clarke RJ (2001) The dipole potential of phospholipid membranes and methods for its detection. Adv Colloid Interface Sci 89:263–281

    Article  PubMed  Google Scholar 

  • Coster HGL, James VJ, Berthet C, Miller A (1981) Location and effect of procaine on lecithin/cholesterol membranes using X-ray diffraction methods. Biochim Biophys Acta (BBA)-Biomembr 641:281–285

    Article  CAS  Google Scholar 

  • Covino BG, Vassallo HG (1976) Local anesthetics: mechanisms of action and clinical use. Grune & Stratton, New York, pp 131–140

    Google Scholar 

  • Darden T, York D, Pedersen L (1993) Particle mesh Ewald: an N·log (N) method for Ewald sums in large systems. J Chem Phys 98:10089–10092

    Article  CAS  Google Scholar 

  • Davis JE, Rahaman O, Patel S (2009) Molecular dynamics simulations of a DMPC bilayer using nonadditive interaction models. Biophys J 96:385–402

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Feller SE (2000) Molecular dynamics simulations of lipid bilayers. Curr Opin Colloid Interface Sci 5:217–223

    Article  CAS  Google Scholar 

  • Flewelling RF, Hubbell WL (1986) The membrane dipole potential in a total membrane potential model. Applications to hydrophobic ion interactions with membranes. Biophys J 49:541

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Franks NP, Lieb WR (1984) Do general anaesthetics act by competitive binding to specific receptors. Nature 310:599–601

    Article  CAS  PubMed  Google Scholar 

  • Freud S (1884) Ueber coca. Centralblatt für die ges Therapie 2:289–314

    Google Scholar 

  • Frisch MJ, Trucks GW, Schlegel HB et al (2004) Gaussian 03. Gaussian, Inc., Wallingford CT

    Google Scholar 

  • Gabdoulline RR, Vanderkooi G, Zheng C (1996) Comparison of the structures of dimyristoylphosphatidylcholine in the presence and absence of cholesterol by molecular dynamics simulations. J Phys Chem 100:15942–15946

    Article  CAS  Google Scholar 

  • Giotta GJ, Chan DS, Wang HH (1974) Binding of spin-labeled local anesthetics to phosphatidylcholine and phosphatidylserine liposomes. Arch Biochem Biophys 163:453–458

    Article  CAS  PubMed  Google Scholar 

  • Goodman LS, Brunton LL, Chabner B, Knollmann BC (2011) Goodman and Gilman’s pharmacological basis of therapeutics. McGraw-Hill, New York

    Google Scholar 

  • Halgren TA, Damm W (2001) Polarizable force fields. Curr Opin Struct Biol 11:236–242

    Article  CAS  PubMed  Google Scholar 

  • Hata T, Matsuki H, Kaneshina S (2000) Effect of local anesthetics on the phase transition temperatures of ether-and ester-linked phospholipid bilayer membranes. Colloids Surf B Biointerfaces 18:41–50

    Article  CAS  Google Scholar 

  • Haydon DA, Hendry BM, Levinson SR, Requena J (1977) Anaesthesia by the n-alkanes. A comparative study of nerve impulse blockage and the properties of black lipid bilayer membranes. Biochim Biophys Acta (BBA)-Biomembr 470:17–34

    Article  CAS  Google Scholar 

  • Hersh EV, Giannakopoulos H, Levin LM et al (2006) The pharmacokinetics and cardiovascular effects of high-dose articaine with 1: 100,000 and 1: 200,000 epinephrine. J Am Dent Assoc 137:1562–1571

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Hoenemann CW, Podranski T, Lo B et al (1998) Local Anesthetic Effects on Thromboxane A ~ 2 Signaling. Anesthesiol THEN HAGERSTOWN- 89:A886

    Article  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • Hoover WG (1985) Canonical dynamics: equilibrium phase-space distributions. Phys Rev A 31:1695

    Article  CAS  Google Scholar 

  • Jalili S, Saeedi M (2016) Study of curcumin behavior in two different lipid bilayer models of liposomal curcumin using molecular dynamics simulation. J Biomol Struct Dyn 34:327–340

    Article  CAS  PubMed  Google Scholar 

  • Kaminoh Y, Inoue T, Ma SM (1988) Membrane-buffer partition coefficients of tetracaine for liquid-crystal and solid-gel membranes estimated by direct ultraviolet spectrophotometry. Biochim Biophys Acta (BBA)-Biomembr 946:337–344

    Article  CAS  Google Scholar 

  • Kelusky EC, Smith IC (1983) Characterization of the binding of the local anesthetics procaine and tetracaine to model membranes of phosphatidylethanolamine: a deuteron nuclear magnetic resonance study. Biochemistry 22:6011–6017

    Article  CAS  PubMed  Google Scholar 

  • Kim B, Young T, Harder E et al (2005) Structure and dynamics of the solvation of bovine pancreatic trypsin inhibitor in explicit water: a comparative study of the effects of solvent and protein polarizability. J Phys Chem B 109:16529–16538

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koch DM, Peslherbe GH (2008) Importance of polarization in quantum mechanics/molecular mechanics descriptions of electronic excited states: NaI (H2O) n photodissociation dynamics as a case study. J Phys Chem B 112:636–649

    Article  CAS  PubMed  Google Scholar 

  • Koubi L, Tarek M, Klein ML, Scharf D (2000) Distribution of halothane in a dipalmitoylphosphatidylcholine bilayer from molecular dynamics calculations. Biophys J 78:800–811

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koubi L, Saiz L, Tarek M et al (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 

  • Kučerka N, Liu Y, Chu N et al (2005) Structure of fully hydrated fluid phase DMPC and DLPC lipid bilayers using X-ray scattering from oriented multilamellar arrays and from unilamellar vesicles. Biophys J 88:2626–2637

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kumar S, Nussinov R (1999) Salt bridge stability in monomeric proteins. J Mol Biol 293:1241–1255

    Article  CAS  PubMed  Google Scholar 

  • Kyrychenko A, Dyubko TS (2008) Molecular dynamics simulations of microstructure and mixing dynamics of cryoprotective solvents in water and in the presence of a lipid membrane. Biophys Chem 136:23–31

    Article  CAS  PubMed  Google Scholar 

  • Lamoureux G, Roux B (2003) Modeling induced polarization with classical drude oscillators: theory and molecular dynamics simulation algorithm. J Chem Phys 119:3025–3039

    Article  CAS  Google Scholar 

  • Lensink MF, Govaerts C, Ruysschaert JM (2010) Identification of specific lipid-binding sites in integral membrane proteins. J Biol Chem 285:10519–10526

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lide DR (2004) CRC handbook of chemistry and physics. CRC Press, Boca Raton

    Google Scholar 

  • Loo DD, Hazama A, Supplisson S et al (1993) Relaxation kinetics of the Na+/glucose cotransporter. Proc Natl Acad Sci 90:5767–5771

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lyubartsev AP, Laaksonen A (2000) M. DynaMix–a scalable portable parallel MD simulation package for arbitrary molecular mixtures. Comput Phys Commun 128:565–589

    Article  CAS  Google Scholar 

  • Lyubartsev AP, Martsinovski AA, Shevkunov SV, Vorontsov-Velyaminov PN (1992) New approach to Monte Carlo calculation of the free energy: method of expanded ensembles. J Chem Phys 96:1776–1783

    Article  CAS  Google Scholar 

  • Lyubartsev AP, Laaksonen A, Vorontsov-Velyaminov PN (1994) Free energy calculations for Lennard-Jones systems and water using the expanded ensemble method A Monte Carlo and molecular dynamics simulation study. Mol Phys 82:455–471

    Article  CAS  Google Scholar 

  • MacKerell AD Jr, Bashford D, Bellott M et al (1998) All-atom empirical potential for molecular modeling and dynamics studies of proteins†. J Phys Chem B 102:3586–3616

    Article  CAS  PubMed  Google Scholar 

  • Maggio B (1999) Modulation of phospholipase A2 by electrostatic fields and dipole potential of glycosphingolipids in monolayers. J Lipid Res 40:930–939

    CAS  PubMed  Google Scholar 

  • Mälkiä A, Murtomäki L, Urtti A, Kontturi K (2004) Drug permeation in biomembranes: in vitro and in silico prediction and influence of physicochemical properties. Eur J Pharm Sci 23:13–47

    Article  PubMed  CAS  Google Scholar 

  • Meyer H (1901) Zur theorie der alkoholnarkose. Arch für Exp Pathol und Pharmakologie 46:338–346

    Article  Google Scholar 

  • Michalet X (2010) Mean square displacement analysis of single-particle trajectories with localization error: Brownian motion in an isotropic medium. Phys Rev E 82:41914

    Article  CAS  Google Scholar 

  • Mojumdar EH, Lyubartsev AP (2010) Molecular dynamics simulations of local anesthetic articaine in a lipid bilayer. Biophys Chem 153:27–35

    Article  CAS  PubMed  Google Scholar 

  • Narahashi T, Yamada M, Frazier DT (1969) Cationic forms of local anaesthetics block action potentials from inside the nerve membrane. Nature 223:748–749

    Article  CAS  PubMed  Google Scholar 

  • Neal MJ, Butler KW, Polnaszek CF, Smith IC (1976) The influence of anesthetics and cholesterol on the degree of molecular organization and mobility of ox brain white matter Lipids in multibilayer membranes: a spin probe study using spectral simulation by the stochastic method. Mol Pharmacol 12:144–155

    CAS  PubMed  Google Scholar 

  • Nosé S (1984) A molecular dynamics method for simulations in the canonical ensemble. Mol Phys 52:255–268

    Article  Google Scholar 

  • Noskov SY, Lamoureux G, Roux B (2005) Molecular dynamics study of hydration in ethanol-water mixtures using a polarizable force field. J Phys Chem B 109:6705–6713

    Article  CAS  PubMed  Google Scholar 

  • Nuss HB, Kambouris NG, Marbán E et al (2000) Isoform-specific lidocaine block of sodium channels explained by differences in gating. Biophys J 78:200–210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Overton CE (1901) Studien über die Narkose zugleich ein Beitrag zur allgemeinen Pharmakologie. Fischer, Frankfurt

    Google Scholar 

  • Papahadjopoulos D, Jacobson K, Poste G, Shepherd G (1975) Effects of local anesthetics on membrane properties I. Changes in the fluidity of phospholipid bilayers. Biochim Biophys Acta (BBA)-Biomembr 394:504–519

    Article  CAS  Google Scholar 

  • Parrinello M, Rahman A (1981) Polymorphic transitions in single crystals: a new molecular dynamics method. J Appl Phys 52:7182–7190

    Article  CAS  Google Scholar 

  • Patel S, Brooks CL III (2006) Fluctuating charge force fields: recent developments and applications from small molecules to macromolecular biological systems. Mol Simul 32:231–249

    Article  CAS  Google Scholar 

  • Pérez-Isidoro R, Sierra-Valdez FJ, Ruiz-Suárez JC (2014) Anesthetic diffusion through lipid membranes depends on the protonation rate. Sci Rep 4:7534

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Porasso RD, Drew Bennett WF, Oliveira-Costa SD, Lopez Cascales JJ (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  PubMed  Google Scholar 

  • Ruetsch YA, Boni T, Borgeat A (2001) From cocaine to ropivacaine: the history of local anesthetic drugs. Curr Top Med Chem 1:175–182

    Article  CAS  PubMed  Google Scholar 

  • Saiz L, Bandyopadhyay S, Klein ML (2002) Towards an understanding of complex biological membranes from atomistic molecular dynamics simulations. Biosci Rep 22:151–173

    Article  CAS  PubMed  Google Scholar 

  • SchuÈttelkopf AW, Van Aalten DMF (2004) PRODRG: a tool for high-throughput crystallography of protein–ligand complexes. Acta Crystallogr Sect D: Biol Crystallogr 60:1355–1363

    Article  CAS  Google Scholar 

  • Scott DB, Jebson PJR, Braid DP et al (1972) Factors affecting plasma levels of lignocaine and prilocaine. Br J Anaesth 44:1040–1049

    Article  CAS  PubMed  Google Scholar 

  • Seelig A (1987) Local anesthetics and pressure: a comparison of dibucaine binding to lipid monolayers and bilayers. Biochim Biophys Acta (BBA)-Biomembr 899:196–204

    Article  CAS  Google Scholar 

  • Seelig A, Allegrini PR, Seelig J (1988) Partitioning of local anesthetics into membranes: surface charge effects monitored by the phospholipid head-group. Biochim Biophys Acta (BBA)-Biomembr 939:267–276

    Article  CAS  Google Scholar 

  • Sigworth FJ (1994) Voltage gating of ion channels. Q Rev Biophys 27:1–40

    Article  CAS  PubMed  Google Scholar 

  • Strichartz GR (1973) The inhibition of sodium currents in myelinated nerve by quaternary derivatives of lidocaine. J Gen Physiol 62:37–57

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Strichartz GR, Ritchie JM (1987) The action of local anesthetics on ion channels of excitable tissues. Local anesthetics. Springer, New York, pp 21–52

    Chapter  Google Scholar 

  • Strichartz GR, Sanchez V, Arthur GR et al (1990) Fundamental properties of local anesthetics. II. Measured octanol: buffer partition coefficients and pKa values of clinically used drugs. Anesth Analg 71:158–170

    Article  CAS  PubMed  Google Scholar 

  • Subbotina JO, Johannes J, Lev B, Noskov SY (2010) Halothane solvation in water and organic solvents from molecular simulations with new polarizable potential function. J Phys Chem B 114:6401–6408

    Article  CAS  PubMed  Google Scholar 

  • Tieleman DP, Marrink SJ, Berendsen HJC (1997) A computer perspective of membranes: molecular dynamics studies of lipid bilayer systems. Biochim Biophys Acta (BBA)-Rev Biomembr 1331:235–270

    Article  CAS  Google Scholar 

  • Tonner PH, Miller KW (1995) Molecular sites of general anaesthetic action on acetylcholine receptors. Eur J Anaesthesiol 12:21–30

    CAS  PubMed  Google Scholar 

  • Toukan K, Rahman A (1985) Molecular-dynamics study of atomic motions in water. Phys Rev B 31:2643

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Ueda I, Hirakawa M, Arakawa K, Kamaya H (1986) Do anesthetics fluidize membranes? Anesthesiology 64:67–71

    Article  CAS  PubMed  Google Scholar 

  • Ueda I, Chiou J-S, Krishna PR, Kamaya H (1994) Local anesthetics destabilize lipid membranes by breaking hydration shell: infrared and calorimetry studies. Biochim Biophys Acta (BBA)-Biomembr 1190:421–429

    Article  CAS  Google Scholar 

  • Van Der Spoel D, Lindahl E, Hess B, et al (2010) Gromacs User Manual version 4.5.4. http://www.gromacs.org/. Accessed 12 July 2016

  • Vorobyov I, Bennett WFD, Tieleman DP et al (2012) The role of atomic polarization in the thermodynamics of chloroform partitioning to lipid bilayers. J Chem Theory Comput 8:618–628

    Article  CAS  PubMed  Google Scholar 

  • Walter A, Gutknecht J (1986) Permeability of small nonelectrolytes through lipid bilayer membranes. J Membr Biol 90:207–217

    Article  CAS  PubMed  Google Scholar 

  • Wang J, Hou T (2011) Application of molecular dynamics simulations in molecular property prediction II: diffusion coefficient. J Comput Chem 32:3505–3519

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang J, Wolf RM, Caldwell JW et al (2004) Development and testing of a general amber force field. J Comput Chem 25:1157–1174

    Article  CAS  PubMed  Google Scholar 

  • Wood I, Pickholz M (2013) Concentration effects of sumatriptan on the properties of model membranes by molecular dynamics simulations. Eur Biophys J 42:833–841

    Article  CAS  PubMed  Google Scholar 

  • Wright SN, Wang SY, Xiao YF, Wang GK (1999) State-dependent cocaine block of sodium channel isoforms, chimeras, and channels coexpressed with the β1 subunit. Biophys J 76:233–245

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yagiela JA, Dowd FJ, Johnson B et al (2010) Pharmacology and therapeutics for dentistry. Elsevier Health Sciences, Amsterdam

    Google Scholar 

  • Yang L, Ahmed A, Sandler SI (2013) Comparison of two simulation methods to compute solvation free energies and partition coefficients. J Comput Chem 34:284–293

    Article  PubMed  CAS  Google Scholar 

  • Zapata-Morin PA, Sierra-Valdez FJ, Ruiz-Suárez JC (2014) The interaction of local anesthetics with lipid membranes. J Mol Graph Model 53:200–205

    Article  CAS  PubMed  Google Scholar 

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  1. Department of Chemistry, K. N. Toosi University of Technology, Tehran, P.O. Box 15875-4416, Iran

    Seifollah Jalili & Marzieh Saeedi

  2. Computational Physical Sciences Research Laboratory, School of Nano-Science, Institute for Research in Fundamental Sciences (IPM), Tehran, P.O. Box 19395-5531, Iran

    Seifollah Jalili

  3. Chemical Physics Theory Group, Department of Chemistry, University of Toronto, 80 Saint George Street, Toronto, Ontario, M5S 3H6, Canada

    Seifollah Jalili

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Jalili, S., Saeedi, M. Study of procaine and tetracaine in the lipid bilayer using molecular dynamics simulation. Eur Biophys J 46, 265–282 (2017). https://doi.org/10.1007/s00249-016-1164-8

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