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http://dx.doi.org/10.5657/KFAS.2016.0815

Molecular Dynamics Simulation Studies of the Effects of the Protonation State of Chitosan in Interactions with Bacterial Membranes  

Truong, Gia Khuong (Interdisciplinary Program of Biomedical, Electrical and Mechanical Engineering, Pukyong National University)
Yi, Myunggi (Department of Biomedical Engineering, Pukyong National University)
Publication Information
Korean Journal of Fisheries and Aquatic Sciences / v.49, no.6, 2016 , pp. 815-822 More about this Journal
Abstract
The cationic biopolymer chitosan has several applications in medicine. Chitosan is the deacetylated derivative of chitin, the second most abundant naturally occurring polymer. Recent studies have investigated the relationship between chitosan and antibacterial activity. However, the molecular interactions and mechanisms have not been detailed. This study used molecular dynamics simulations to study interactions between chitosan and anionic bacterial membranes (POPE-POPG) and electrically neutral non-bacterial membranes (POPC). We calculated the free energy using umbrella sampling to compare the interactions between membranes and chitosan in different protonation states. Fully protonated chitosan interacted most strongly with the bacterial membranes, but weakly with non-bacterial membranes. These results suggest that electrostatic interactions are the main mechanism of the antibacterial activity of chitosan, and they provide insights into the design of novel antibacterial and antimicrobial agents.
Keywords
Chitosan; Antibacterial activity; Molecular dynamics; Electrostatic interaction;
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1 Berweger CD, van Gunsteren WF and Müller-Plathe F. 1995. Force field parametrization by weak coupling. Re-engineering SPC water. Chem Phys Lett 232, 429-436. http://dx.doi.org/10.1016/0009-2614(94)01391-8.   DOI
2 Choi B-K, Kim K-Y, Yoo Y-J, Oh S-J, Choi J-H and Kim C-Y. 2001. In vitro antimicrobial activity of a chitooligosaccharide mixture against Actinobacillus actinomycetemcomitans and Streptococcus mutans. Int J Antimicrob Agents 18, 553-557. http://dx.doi.org/10.1016/S0924-8579(01)00434-4.   DOI
3 Elmore DE. 2006. Molecular dynamics simulation of a phosphatidylglycerol membrane. FEBS letters 580, 144-148. http://dx.doi.org/10.1016/j.febslet.2005.11.064.   DOI
4 Essmann U, Perera L, Berkowitz ML, Darden T, Lee H and Pedersen LG. 1995. A smooth particle mesh Ewald method. J Chem Phys 103, 8577. http://dx.doi.org/10.1063/1.470117.   DOI
5 Gazit E, Miller IR, Biggin PC, Sansom MSP and Shai Y. 1996. Structure and orientation of the mammalian antibacterial peptide cecropin P1 within phospholipid membranes. J Mol Biol 258, 860-870. http://dx.doi.org/10.1006/jmbi.1996.0293.   DOI
6 Gottenbos B, Grijpma DW, van der Mei HC, Feijen J and Busscher HJ. 2001. Antimicrobial effects of positively charged surfaces on adhering Gram-positive and Gram-negative bacteria. J Antimicr Chemother 48, 7-13.   DOI
7 Hallock KJ, Lee D-K, Omnaas J, Mosberg HI and Ramamoorthy A. 2002. Membrane composition determines Pardaxin's mechanism of lipid bilayer disruption. Biophys J 83, 1004-1013. http://dx.doi.org/10.1016/S0006-3495(02)75226-0.   DOI
8 Hong C, Tieleman DP and Wang Y. 2014. Microsecond molecular dynamics simulations of lipid mixing. Langmuir 30, 11993-12001. http://dx.doi.org/10.1021/la502363b.   DOI
9 Kim I-Y, Seo S-J, Moon H-S, Yoo M-K, Park I-Y, Kim B-C and Cho C-S. 2008. Chitosan and its derivatives for tissue engineering applications. Biotechnol Adv 26, 1-21. http://dx.doi.org/10.1016/j.biotechadv.2007.07.009.   DOI
10 Hub JS, de Groot BL and van der Spoel D. 2010. A free weighted histogram analysis implementation including robust error and autocorrelation estimates. J Chem Theory Comput 6, 3713-3720. http://dx.doi.org/10.1021/ct100494z.   DOI
11 Matsuzaki K. 2009. Control of cell selectivity of antimicrobial peptides. Biochimica et biophysica acta 1788, 1687-1692. http://dx.doi.org/10.1016/j.bbamem.2008.09.013.   DOI
12 Krajewska B, Wydro P and Janczyk A. 2011. Probing the modes of antibacterial activity of chitosan. Effects of pH and molecular weight on chitosan interactions with membrane lipids in Langmuir films. Biomacromolecules 12, 4144-4152. http://dx.doi.org/10.1021/bm2012295.   DOI
13 Kumar RMNV, Muzzarelli RAA, Muzzarelli C, Sashiwa H and Domb AJ. 2005. Chitosan chemistry and pharmaceutical perspectives. ChemInform 36, 6017-6084. http://dx.doi.org/10.1002/chin.200511296.   DOI
14 Mani R, Cady SD, Tang M, Waring AJ, Lehrer RI and Hong M. 2006. Membrane-dependent oligomeric structure and pore formation of a ${\beta}1$-hairpin antimicrobial peptide in lipid bilayers from solid-state NMR. Proc Natl Acad Sci USA 103, 16242-16247. http://dx.doi.org/10.1073/pnas.0605079103.   DOI
15 Niaounakis M. 2015. Biopolymers: Applications and trends. Elsevier, Amsterdam. http://dx.doi.org/10.1016/B978-0-323-35399-1.09001-3.   DOI
16 Oostenbrink C, Villa A, Mark AE and Gunsteren WF. 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, 1656-1676. http://dx.doi.org/10.1002/jcc.20090.   DOI
17 Pomastowski P et al. 2016. Silver-Lactoferrin Nanocomplexes as a potent antimicrobial agent. J Am Chem Soc 138, 7899-7909. http://dx.doi.org/10.1021/jacs.6b02699.   DOI
18 Parkin J, Chavent M and Khalid S. 2015. Molecular Simulations of Gram-Negative Bacterial Membranes: A Vignette of Some Recent Successes. Biophys J 109, 461-468. http://dx.doi.org/10.1016/j.bpj.2015.06.050.   DOI
19 Picas L, Carretero-Genevrier A, Montero TM, Vazquez-Ibar JL, Seantier B, Milhiet P-E and Hernandez-Borrell J. 2010a. Preferential insertion of lactose permease in phospholipid domains: AFM observations. BBA-Biomembranes 1798, 1014-1019. http://dx.doi.org/10.1016/j.bbamem.2010.01.008.   DOI
20 Picas L, Montero TM, Morros A, Vazquez-Ibar JL and Hernandez-Borrell J. 2010b. Evidence of phosphatidylethanolamine and phosphatidylglycerol presence at the annular region of lactose permease of Escherichia coli. BBA-Biomembranes 1798, 291-296. http://dx.doi.org/10.1016/j.bbamem.2009.06.024   DOI
21 Pouny Y, Rapaport D, Mor A, Nicolas P and Shai Y. 1992. Interaction of antimicrobial dermaseptin and its fluorescently labeled analogues with phospholipid membranes. Biochemistry 31, 12416-12423.   DOI
22 Schuttelkopf AW and van Aalten DM. 2004. PRODRG: a tool for high-throughput crystallography of protein-ligand complexes. Acta Crystallogr Sect D-Biol Crystallogr 60, 1355-1363. http://dx.doi.org/10.1107/S0907444904011679.   DOI
23 Silhavy TJ, Kahne D and Walker S. 2010. The bacterial cell envelope. Cold Spring Harbor perspectives in biology 2, a000414. http://dx.doi.org/10.1101/cshperspect.a000414.   DOI
24 Taha SMA and Swailam HMH. 2002. Antibacterial activity of chitosan against Aeromonas hydrophila. Food / Nahrung 46, 337-340. http://dx.doi.org/10.1002/1521-3803(20020901)46:5<337::AID-FOOD337>3.0.CO;2-3.   DOI
25 Toukmaji A, Sagui C, Board J and Darden T. 2000. Efficient particle-mesh Ewald based approach to fixed and induced dipolar interactions. J Chem Phys 113, 10913. http://dx.doi.org/10.1063/1.1324708.   DOI
26 Taveira SF, Nomizo A and Lopez R. 2009. Effect of the iontophoresis of a chitosan gel on doxorubicin skin penetration and cytotoxicity. J Control Release 134, 35-40. http://dx.doi.org/10.1016/j.jconrel.2008.11.002.   DOI
27 Tham PTH and Yi M. 2015. Selectivity of the ${\alpha}6$ nAChR subunit on ${\alpha}$-conotoxin BuIA studied by molecular dynamics simulations. Korean J Fish Aquat Sci 48, 071-075. http://dx.doi.org/10.5657/KFAS.2015.0071.   DOI
28 Torrie GM and Valleau JP. 1977. Nonphysical sampling distributions in Monte Carlo free-energy estimation: Umbrella sampling. J Comput Phys 23, 187-199. http://dx.doi.org/10.1016/0021-9991(77)90121-8.   DOI
29 Tsai GJ and Su WH. 1999. Antibacterial activity of shrimp chitosan against Escherichia coli. J Food Prot 62, 239-243.   DOI
30 Van Der Spoel D, Lindahl E, Hess B, Groenhof G, Mark AE and Berendsen HJ. 2005. GROMACS: fast, flexible, and free. J Computat Chem 26, 1701-1718. http://dx.doi.org/10.1002/jcc.20291.   DOI
31 Vinsova J and Vavrikova E. 2008. Recent advances in drugs and prodrugs design of chitosan. Curr Pharm Des 14, 1311-1326. http://dx.doi.org/10.2174/138161208799316410.   DOI
32 Wimley WC. 2010. Describing the mechanism of antimicrobial peptide action with the interfacial activity model. ACS Chem Biol 5, 905-917. http://dx.doi.org/10.1021/cb1001558.   DOI
33 Yi M, Nymeyer H and Zhou H-X. 2008. Test of the Gouy-Chapman theory for a charged lipid membrane against explicitsolvent molecular dynamics simulations. Phys Rev Lett 101, 38103. http://dx.doi.org/10.1103/PhysRevLett.101.038103.   DOI