* Corresponding Author
Structure of the Cyclic, Cationic Antimicrobial Peptide (KKWWKF) in Octanol Solution: in silico Approach
https://doi.org/10.22146/ijc.49190 Seyed Hassan Mortazavi(1), Mohammad Reza Bozorgmehr(2*), Mohammad Momen Heravi(3)
(1) Department of Chemistry, Mashhad Branch, Islamic Azad University, Mashhad, Iran
(2) Department of Chemistry, Mashhad Branch, Islamic Azad University, Mashhad, Iran
(3) Department of Chemistry, Mashhad Branch, Islamic Azad University, Mashhad, Iran
(*) Corresponding Author
Abstract
Understanding the mechanism of antimicrobial activity of cyclo-peptides helps to design new drugs based on these compounds. A common aspect of the mechanisms provided for the creation of antimicrobial activity of cyclo-peptides is their interaction with cell membranes. On the other hand, the octanol/water system is a good mimic of the water/membrane interface. Here, the conformational structure of the very short sequences cationic hexapeptide cyclo (Lys-Lys-Trp-Trp-Lys-Phe) has been studied in different concentrations of octanol by molecular dynamics simulation. The concentration of alcohol in the range of experimental concentrations of octanol was considered. The results obtained from calculating the radial distribution function show that the interaction of the peptide with octanol is a mixted of interactions between charged residues with octanol and the interaction of aromatic residues with octanol. These results are in agreement with experimental observations. Also, Lys5 plays a greater role than Lys1 and Lys2 in the interactions with octanol.
Keywords
Full Text:
Full Text PDFReferences
[1] Hancock, R.E., and Sahl, H.G., 2006, Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies, Nat. Biotechnol., 24 (12), 1551–1557.
[2] Reddy, K.V.R., Yedery, R.D., and Aranha, C., 2004, Antimicrobial peptides: Premises and promises, Int. J. Antimicrob. Agents, 24 (6), 536–547.
[3] Yount, N.Y., and Yeaman, M.R., 2004, Multidimensional signatures in antimicrobial peptides, Proc. Natl. Acad. Sci. U.S.A., 101 (19), 7363–7368.
[4] Appelt, C., Schrey, A.K., Söderhäll, J.A., and Schmieder, P., 2007, Design of antimicrobial compounds based on peptide structures, Bioorg. Med. Chem. Lett., 17 (8), 2334–2337.
[5] Marr, A.K., Gooderham, W.J., and Hancock, R.E., 2006, Antibacterial peptides for therapeutic use: Obstacles and realistic outlook, Curr. Opin. Pharmacol., 6 (5), 468–472.
[6] Zasloff, M., 2002, Antimicrobial peptides of multicellular organisms, Nature, 415 (6870), 389–395.
[7] Fjell, C.D., Hiss, J.A., Hancock, R.E., and Schneider, G., 2012, Designing antimicrobial peptides: Form follows function, Nat. Rev. Drug Discovery, 16 (11), 37–51.
[8] Finger, S., Kerth, A., Dathe, M., and Blume, A., 2015, The efficacy of trivalent cyclic hexapeptides to induce lipid clustering in PG/PE membranes correlates with their antimicrobial activity, Biochim. Biophys. Acta, Biomembr., 1848 (11), 2998–3006.
[9] Chan, D.I., Prenner, E.J., and Vogel, H.J., 2006, Tryptophan- and arginine-rich antimicrobial peptides: Structures and mechanisms of action, Biochim. Biophys. Acta, Biomembr., 1758 (9), 1184–1202.
[10] Hale, J.D., and Hancock, R.E., 2007, Alternative mechanisms of action of cationic antimicrobial peptides on bacteria, Expert Rev. Anti Infect. Ther., 5 (6), 951–959.
[11] Wessolowski, A., Bienert, M., and Dathe, M., 2004, Antimicrobial activity of arginine‐and tryptophan‐rich hexapeptides: The effects of aromatic clusters, D‐amino acid substitution and cyclization, J. Pept. Res., 64 (4), 159–169.
[12] Lai, Y., and Gallo, R.L., 2009, AMPed up immunity: how antimicrobial peptides have multiple roles in immune defense, Trends Immunol., 30 (3), 131–141.
[13] Shai, Y., 1999, Mechanism of the binding, insertion and destabilization of phospholipid bilayer membranes by α-helical antimicrobial and cell non-selective membrane-lytic peptides, Biochim. Biophys. Acta, Biomembr., 1462 (1-2), 55–70.
[14] Marchal, D., Boireau, W., Laval, J.M., Moiroux, J., and Bourdillon, C., 1998, Electrochemical measurement of lateral diffusion coefficients of ubiquinones and plastoquinones of various isoprenoid chain lengths incorporated in model bilayers, Biophys. J., 74 (4), 1937–1948.
[15] Shepherd, C.M., Vogel, H.J., and Tieleman, D.P., 2003, Interactions of the designed antimicrobial peptide MB21 and truncated dermaseptin S3 with lipid bilayers: Molecular-dynamics simulations, Biochem. J., 370 (1), 233–243.
[16] Jean-François, F., Elezgaray, J., Berson, P., Vacher, P., and Dufourc, E.J., 2008, Pore formation induced by an antimicrobial peptide: Electrostatic effects, Biophys. J., 95 (12), 5748–5756.
[17] Wang, Y., Schlamadinger, D.E., Kim, J.E., and McCammon, J.A., 2012, Comparative molecular dynamics simulations of the antimicrobial peptide CM15 in model lipid bilayers, Biochim. Biophys. Acta, Biomembr., 1818 (5), 1402–1409.
[18] Appelt, C., Wessolowski, A., Söderhäll, J.A., Dathe, M., and Schmieder, P., 2005, Structure of the antimicrobial, cationic hexapeptide cyclo (RRWWRF) and its analogues in solution and bound to detergent micelles, ChemBioChem, 6 (9), 1654–1662.
[19] Abraham, M.J., van der Spoel, D., Lindahl, E., Hess, B., and the GROMACS development team, 2016, GROMACS User Manual version 5.1.2, www.gromacs.org.
[20] van Gunsteren, W.F., Billeter, S., Eising, A.A., Hunenberger, P.H., Krüger, P., Mark, A.E., Scott, W.R.P., and Tironi, I.G., 1996, Biomolecular simulation: The GROMOS96 manual and user guide, Hochschulverlag AG an der ETH Zürich, Zürich, Switzerland.
[21] Hess, B., Bekker, H., Berendsen, H.J.C., and Fraaije, J.G.E.M., 1997, LINCS: A linear constraint solver for molecular simulations, J. Comput. Chem., 18 (12), 1463–1472.
[22] Miyamoto, S., and Kollman, P.A., 1992, Settle: An analytical version of the SHAKE and RATTLE algorithm for rigid water models, J. Comput. Chem., 13 (8), 952–962.
[23] Arouri, A., Dathe, M., and Blume, A., 2009, Peptide induced demixing in PG/PE lipid mixtures: A mechanism for the specificity of antimicrobial peptides towards bacterial membranes?, Biochim. Biophys. Acta, Biomembr., 1788 (3), 650–659.
[24] Wadhwani, P., Epand, R.F., Heidenreich, N., Bürck, J., Ulrich, A.S., and Epand, R.M., 2012, Membrane-active peptides and the clustering of anionic lipids, Biophys. J., 103 (2), 265–274.
[25] Dathe, M., Nikolenko, H., Klose, J., and Bienert, M., 2004, Cyclization increases the antimicrobial activity and selectivity of arginine-and tryptophan-containing hexapeptides, Biochemistry, 43 (28), 9140–9150.
[26] Jahanbin, F., Bozorgmehr, M.R., Morsali, A., and Beyramabadi, S.A., 2019, The effect of different alcohols on the Asp23-Lys28 and Asp23-Ala42 salt bridges of the most effective peptide in Alzheimer's disease: Molecular dynamics viewpoints, J. Mol. Graphics Modell., 86, 199–208.
[27] Bozorgmehr, M.R., and Monhemi, H., 2015, How can a free amino acid stabilize a protein? Insights from molecular dynamics simulation, J. Solution Chem., 44 (1), 45–53.
[28] Housaindokht, M.R., Bozorgmehr, M.R., and Monhemi, H., 2012, Structural behavior of Candida antarctica lipase B in water and supercritical carbon dioxide: A molecular dynamic simulation study, J. Supercrit. Fluids, 63, 180–186.
[29] Almeida, P.F., and Pokorny, A., 2009, Mechanisms of antimicrobial, cytolytic, and cell-penetrating peptides: From kinetics to thermodynamics, Biochemistry, 48 (34), 8083–8093.
[30] Brune, D., and Kim, S., 1993, Predicting protein diffusion coefficients, Proc. Natl. Acad. Sci. U.S.A., 90 (9), 3835–3839.
[31] Frenkel, D., and Smit, B., 2002, Understanding Molecular Simulation: From Algorithms to Applications, 2nd Ed., Academic Press, San Diego, CA.
DOI: https://doi.org/10.22146/ijc.49190
Article Metrics
Abstract views : 1803
| 
views : 1539
Copyright (c) 2020 Indonesian Journal of Chemistry
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Indonesian Journal of Chemistry (ISSN 1411-9420 /e-ISSN 2460-1578) - Chemistry Department, Universitas Gadjah Mada, Indonesia.