An investigation of molecular dynamics simulation and molecular docking: Interaction of citrus flavonoids and bovine β-lactoglobulin in focus
Authors: 
M. Sahihi, Y. GhayebAuthors Info & Claims
M. Sahihi, Y. GhayebAuthors Info & ClaimsPages 44 - 50
Abstract
Citrus flavonoids are natural compounds with important health benefits. The study of their interaction with a transport protein, such as bovine @b-lactoglobulin (BLG), at the atomic level could be a valuable factor to control their transport to biological sites. In the present study, molecular docking and molecular dynamics simulation methods were used to investigate the interaction of hesperetin, naringenin, nobiletin and tangeretin as citrus flavonoids and BLG as transport protein. The molecular docking results revealed that these flavonoids bind in the internal cavity of BLG and the BLG affinity for binding the flavonoids follows naringenin>hesperetin>tangeretin>nobiletin. The docking results also indicated that the BLG-flavonoid complexes are stabilized through hydrophobic interactions, hydrogen bond interactions and @p-@p stacking interactions. The analysis of molecular dynamics (MD) simulation trajectories showed that the root mean square deviation (RMSD) of various systems reaches equilibrium and fluctuates around the mean value at various times. Time evolution of the radius of gyration, total solvent accessible surface of the protein and the second structure of protein showed as well that BLG and BLG-flavonoid complexes were stable around 2500ps, and there was not any conformational change as for BLG-flavonoid complexes. Further, the profiles of atomic fluctuations indicated the rigidity of the ligand binding site during the simulation.
References
[1]
vanAcker, F.A., Schouten, O., Haenen, G.R., vanderVijgh, W.J. and Bast, A., Flavonoids can replace alpha-tocopherol as an antioxidant. FEBS Lett. v473. 145
[2]
Antioxidant activity of citrus limonoids, flavonoids, and coumarins. J. Agric. Food Chem. v53 i2009.
[3]
Kawaii, S., Tomono, Y., Katase, E., Ogawa, K. and Yano, M., Quantitation of flavonoid constituents in citrus fruits. J. Agric. Food Chem. v47. 3565
[4]
Pszczola, D.E., Natural colors: pigments of imagination. Food Technol. v52. 70
[5]
Cooray, H.C., Janvilisri, T., vanVeen, H.W., Hladky, S.B. and Barrand, M.A., Interaction of the breast cancer resistance protein with plant polyphenols. Biochem. Biophys. Res. Commun. v317. 269
[6]
Xu, C., Chen, J., Zhang, J., Hu, X., Zhou, X., Lu, Z. and Jiang, H., Naringenin inhibits angiotensin II-induced vascular smooth muscle cells proliferation and migration and decreases neointimal hyperplasia in balloon injured rat carotid arteries through suppressing oxidative stress. Biol. Pharm. Bull. v36. 1549
[7]
Waheed, A., Ludtmann, M.H.R., Pakes, N., Robery, S., Kuspa, A., Dinh, C., Baines, D., Williams, R.S.B and Carew, M.A., Naringenin inhibits the growth of Dictyostelium and MDCK-derived cysts in a polycystin-2 (TRPP2)-dependent manner. Br. J. Pharmacol. v171. 2659
[8]
Deng, W., Jiang, D., Fang, Y., Zhou, H., Cheng, Z., Lin, Y., Zhang, R., Zhang, J., Pu, P., Liu, Y., Bian, Z. and Tang, Q., Hesperetin protects against cardiac remodelling induced by pressure overload in mice. J. Mol. Hist. v44. 575
[9]
Wang, J., Zhu, H., Yang, Z. and Liu, Z., Antioxidative effects of hesperetin against lead acetate-induced oxidative stress in rats. Indian J. Pharmacol. v45 i395.
[10]
Yoshigai, E., Machida, T., Okuyama, T., Mori, M., Murase, H., Yamanishi, R., Okumura, T., Ikeya, Y., Nishino, H. and Nishizawa, M., Citrus nobiletin suppresses inducible nitric oxide synthase gene expression in interleukin-1ß-treated hepatocytes. Biochem. Biophys. Res. Commun. v439. 54
[11]
Henrotin, Y., Lambert, C., Couchourel, D., Ripoll, C. and Chiotelli, E., Nutraceuticals: do they represent a new era in the management of osteoarthritis? A narrative review from the lessons taken with five products. Osteoarthr. Cartilage. v19. 1
[12]
Vaiyapuri, S., Marfoua, S.A., Moraes, L.A., Sage, T., Lewis, K.R., Jones, C.I. and Gibbins, J.M., Tangeretin regulates platelet function through inhibition of phosphoinositide 3-kinase and cyclic nucleotide signaling. Arterioscler. Thromb. Vasc. Biol. v33. 2740
[13]
Chong, S.Y., Wu, M.Y. and Lo, Y.C., Tangeretin sensitizes SGS1-deficient cells by inducing DNA damage. J. Agric. Food Chem. v61. 6376
[14]
The lipocalin protein family: structural and sequence overview. Biochim. Biophys. Acta. v1482. 9
[15]
Schlehuber, S. and Skerra, A., Lipocalins in drug discovery: from natural ligand-binding proteins to 'anticalins'. Drug Discov. Today. v10. 23
[16]
Sawyer, L. and Kontopidis, G., The core lipocalin, bovine ß-lactoglobulin. Biochim. Biophys. Acta. v1482. 136
[17]
Dong, A., Matsuura, J., Allison, S.D., Chrisman, E., Manning, M.C. and Carpenter, J.F., Infrared and circular dichroism spectroscopic characterization of structural differences between ß-lactoglobulin A and B. Biochemistry. v35. 1450
[18]
Brownlow, S., Cabral, J.H.M., Cooper, R., Flwoer, D.R., Yewdall, S.J., Polikarpov, I., North, A.C.T. and Sawyer, L., Bovine {beta}-lactoglobulin at 1.8í resolution-still an enigmatic lipocalin. Structure. v5. 481
[19]
Kontopidis, G., Holt, C. and Sawyer, L., The ligand-binding site of bovine {beta}-lactoglobulin: evidence for a function?. J. Mol. Biol. v318. 1043
[20]
Kontopidis, G., Holt, C. and Sawyer, L., {beta}-Lactoglobulin: binding properties, structure, and function. J. Dairy Sci. v87. 785
[21]
Wu, S.Y., Pérez, M.D., Puyol, P. and Sawyer, L., ß-Lactoglobulin binds palmitate within its central cavity. J. Biol. Chem. v274. 170
[22]
Bohin, M.C., Vincken, J.P., van der Hijden, H.T.W.M. and Gruppen, H., Efficacy of food proteins as carriers for flavonoids. J. Agric. Food Chem. v60. 4136
[23]
Sahihi, M., Heidari-Koholi, Z. and Bordbar, A.K., The interaction of polyphenol flavonoids with ß-lactoglobulin: molecular docking and molecular dynamics simulation studies. J. Macromol. Sci. B: Phys. v51. 2311
[24]
M.A. Thompson, ArgusLab 4.0, Planaria Software LLC, Seattle, {http://www.ArgusLab.com}.
[25]
M.A. Thompson, molecular docking using ArgusLab: an efficient shape-based search algorithm and the AScore scoring function. Poster presentation, Fall ACS meeting, Philadelphia, 2004.
[26]
Nikolic, K., Filipic, S. and Agbaba, D., QSAR study of imidazoline antihypertensive drugs. Bioorg. Med. Chem. v16. 7134
[27]
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.J., Windus, T.L., Dupuis, M. and Montgomery, J.A., General atomic and molecular electronic structure system. J. Comput. Chem. v14. 1347
[28]
Berendsen, H.J.C., Van der Spoel, D. and Van Drunen, R., GROMACS: a message-passing parallel molecular dynamics implementation. Comput. Phys. Commun. v91. 43
[29]
Lindah, E., Hess, B. and Van der Spoel, D., GROMACS 3.0: a package for molecular simulation and trajectory analysis. J. Mol. Model. v7. 306
[30]
Van Gunsteren, W.F., Billeter, S.R., Eising, A.A., Hünenberger, P.H., Krüger, P.K.H.C., Mark, A.E., Scott, W.R.P. and Tironi, I.G., Biomolecular Simulation: The GROMOS96 Manual and User Guide. 1996. Vdf Hochschulverlag AG, Zürich.
[31]
Van Gunsteren, W.F., Daura, X. and Mark, A.E., Encyclopedia of Computational Chemistry. 1998. Wiley and Sons, P. Von Rague Schleyer, Chichester, UK.
[32]
Schuttelkopf, A.W. and Van Aalten, D.M.F., PRODRG: a tool for high-throughput crystallography of protein-ligand complexes. Acta Crystallogr. v60. 1355
[33]
Berendsen, H.J.C., Postma, J.P.M., Van Gunstetren, W.F. and Hermans, J., Intermolecular Forces. 1981. B. Pullman, Reidel, Dordrecht, The Netherlands.
[34]
Berendsen, H.J.C., Postma, J.P.M., Van Gunsteren, W.F., DiNola, A. and Haak, J.R., Molecular dynamics with coupling to an external bath. J. Chem. Phys. v81. 3684
[35]
Darden, T., York, D. and Pedersen, L., Particle mesh Ewald: an Nlog(N) method for Ewald sums in large systems. J. Chem. Phys. v98. 10089
[36]
Essmann, U., Perera, L., Berkowitz, M.L., Darden, T., Lee, H. and Pedersen, L.G., A smooth particle mesh Ewald method. J. Chem. Phys. v103. 8577
[37]
Roufik, S., Gauthier, S.F., Leng, X.J. and Turgeon, S.L., Thermodynamics of binding interactions between bovine ß-lactoglobulin A and the antihypertensive peptide ß-Lg f142-148. Biomacromolecules. v7. 419
[38]
Dissertation Etude de I'agr¿egation et de la g¿elification des prot¿eines globulaires: application 'a la beta-Lactoglobuline. 1994. Facult¿e des Science et des Techniques, France, Universit¿e de Nantes.
[39]
Riihimäki, L.H., Vainio, M.J., Heikura, J.M., Valkonen, K.H., Virtanen, V.T. and Vuorela, P.M., Binding of phenolic compounds and their derivatives to bovine and reindeer ß-lactoglobulin. J. Agric. Food Chem. v56. 7721
- An investigation of molecular dynamics simulation and molecular docking: Interaction of citrus flavonoids and bovine β-lactoglobulin in focus
Recommendations
Structure-based design and evaluation of novel N-phenyl-1H-indol-2-amine derivatives for fat mass and obesity-associated (FTO) protein inhibition
Display Omitted N-phenyl-1H-indol-2-amine was selected as a base for novel FTO protein inhibitors.Designed ligands were studied by molecular docking and dynamic simulation approach.Hydroxyl (OH) and carbonyl (CO) group of ligand played a key role in FTO ...
Cavities create a potential back door in epoxide hydrolase Rv1938 from Mycobacterium tuberculosis-A molecular dynamics simulation study
Display Omitted MD simulation of epoxide hydrolase, Rv1938 from Mtb was carried out for 100ns.Additional new cavities apart from the substrate binding pocket have been identified.These cavities which are located behind the active site may behave as a ...
In silico 3-D structure prediction and molecular docking studies of inosine monophosphate dehydrogenase from Plasmodium falciparum
Display Omitted Growing resistance in malarial parasites, particularly in Plasmodium falciparum needs for development of novel drug targets.Inosine monophosphate dehydrogenase (IMPDH) is an important target for antimalarial drug discovery.A homology ...
Comments
Information & Contributors
Information
Published In
Copyright © Elsevier Ltd © 2014.
Publisher
Pergamon Press, Inc.
United States
Publication History
Published: 01 August 2014
Author Tags
Qualifiers
- Article
Contributors
Other Metrics
Bibliometrics & Citations
Bibliometrics
Article Metrics
- 0Total Citations
- 0Total Downloads
- Downloads (Last 12 months)0
- Downloads (Last 6 weeks)0
Reflects downloads up to 03 Jan 2025