Moscow, Moscow, Russian Federation
Moscow, Russian Federation
Moscow, Moscow, Russian Federation
In this work, the influence of orcinol (3,5-dihydroxytoluene; 5-methylresorcinol) on model membranes of a gram-negative bacterial cell of Escherichia coli and the migration of orcinol molecules through model membranes and through the pores of the outer membrane formed by porins were investigated using the methods of classical molecular dynamics. Both the inner membrane leaflets and the inner leaflet of the outer membrane were modeled as mixed layers of 75% POPE / 25% POPG lipids. The outer leaflet of the outer membrane was composed of lipopolysaccharides. The dynamics of model membranes in the presence of orcinol was studied. Using the potential of mean force, the free energy profiles of migration of the orcinol molecule through the porin channel and the membrane were determined. It was found that the main mechanism of migration of orcinol molecules into the cell is diffusion through bilayers. It has been shown that orcinol molecules can both penetrate into the cell through membranes for interaction with intracellular structures, and can easily integrate into bilayers, changing their physicochemical parameters.
5-methylresorcinol, orcinol, E. coli membrane, molecular dynamics, migration of small molecules through the bacterial membrane
1. Krupyanskiy Yu.F., Noks P.P., Loyko N.G. i dr. Vliyanie himicheskih shaperonov na svoystva lizocima i belka reakcionnogo centra bakteriy Rhodobacter sphaeroides. Biofizika, 2011, t. 56, № 1, c. 13-30. @@Krupyanskij Yu.F., Noks P.P., Lojko N.G. et al. Vliyanie himicheskih shaperonov na svojstva lizocima i belka reakcionnogo centra bakterij Rhodobacter sphaeroides. Biofizika, 2011, vol. 56, no. 1, pp. 13-30. (In Russ.)
2. Tereshkina K.B., Stepanov A.S., Sinicyn D.O., Krupyanskiy Yu.F. Vliyanie malyh ligandov i ih kompleksov na svoystva belka lizocima. Himicheskaya fizika, 2014, t. 33, № 7, c. 64-73. @@Tereshkina K.B., Stepanov A.S., Sinicyn D.O., Krupyanskij YU.F. Vliyanie malyh ligandov i ih kompleksov na svojstva belka lizocima. Himicheskaya fizika, 2014, vol. 33, no. 7, pp. 64-73. (In Russ.)
3. Granovsky A.A. Firefly version 8. www http://classic.chem.msu.su/gran/firefly/index.html
4. Schmidt M.W., Baldridge K.K., Boatz J.A., Elbert S.T., Gordon M.S., Jensen J.H., Koseki S., Matsunaga N., Nguyen K.A., Su S., Windus T.L., Dupuis M., Montgomery J.A. General atomic and molecular electronic structure system. J.Comput.Chem., 1993, vol. 14, pp. 1347-1363. DOI:https://doi.org/10.1002/jcc.540141112.
5. Foresman J.B., Frisch A. Exploring chemistry with electronic structure methods 2ed. Gaussian, Inc. Pittsburgh, PA, 1996, pp. 107-116.
6. Warren E. Levinson, Review of Medical Microbiology and Immunology, 11th Edition. Publisher: McGraw-Hill Medical, 2010, 640 p.
7. Sohlenkamp C., Geiger O. Bacterial membrane lipids: diversity in structures and pathways. FEMS Microbiology Reviews, 2016, vol. 40, iss. 1, pp. 133-159. DOI:https://doi.org/10.1093/femsre/fuv008.
8. Lee J., Cheng X., Swails J.M., Yeom M.S., Eastman P.K., Lemkul J.A., Wei S., Buckner J., Jeong J.C., Qi Y., Jo S., Pande V.S., Case D.A., Brooks C.L. III, MacKerell A.D. Jr, Klauda J.B., Im W. CHARMM-GUI Input Generator for NAMD, GROMACS, AMBER, OpenMM, and CHARMM/OpenMM Simulations using the CHARMM36 Additive Force Field. J. Chem. Theory Comput., 2016, vol. 12, pp. 405-413. DOI:https://doi.org/10.1021/acs.jctc.5b00935.
9. Oursel D., Loutelier-Bourhis C., Orange N., Chevalier S., Norris V., Lange C.M. Lipid composition of membranes of Escherichia coli by liquid chromatography/tandem mass spectrometry using negative electrospray ionization. Rapid Commun. Mass Spectrom., 2007, vol. 21, no. 20, pp. 1721-1728. DOI:https://doi.org/10.1002/rcm.3013.
10. Oursel D., Loutelier-Bourhis C., Orange N., Chevalier S., Norris V., Lange C.M. Identification and Relative Quantification of Fatty Acids in Escherichia Coli Membranes by Gas Chromatography/Mass Spectrometry. Rapid Commun Mass Spectrom, 2007, vol. 21, no. 20, pp. 3229-3233. DOI:https://doi.org/10.1002/rcm.3177.
11. Frauenfeld J., Gumbart J., van der Sluis E.O., Funes S., Gartmann M., Beatrix B., Mielke T., Berninghausen O., Becker T., Schulten K., Beckmann R., Cryo E.M. structure of the ribosome-SecYE complex in the membrane environment. Nat. Struct. Mol. Biol, 2011, vol. 18, pp. 614-621.
12. Hess B., Kutzner C., van der Spoel D., Lindahl E. GROMACS 4: Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation. J. Chem. Theory Comput., 2008, vol. 4, pp. 435, DOI:https://doi.org/10.1021/ct700301q.
13. Ivani I., Dans P.D., Noy A. et al. Parmbsc1: a refined force field for DNA simulations. Nat Methods, 2015, vol. 13, no. 1, p. 55. DOI :https://doi.org/10.1038/nmeth.3658.
14. Yildiz O., Vinothkumar K.R., Goswami P., Kühlbrandt W. Structure of the monomeric outer-membrane porin OmpG in the open and closed conformation [published correction appears in EMBO J. 2006 Nov 1;25(21):5240]. EMBO J., 2006, vol. 25, no. 15, pp. 3702-3713. DOI:https://doi.org/10.1038/sj.emboj.7601237.
