Molecular Docking Affinity Comparison of Curcumin and Nano-micelled Curcumin with Natural Sea Salt on Transthyretin

울금의 주요 성분인 커큐민과 나노 마이셀링 기법 적용 염화 커큐민의 트랜스타이레틴 활성 부위에 대한 결합 친화도 비교분석

Kim, Dong-Chan;Song, Pyo

  • Received : 2016.01.19
  • Accepted : 2016.02.12
  • Published : 2016.02.25


In this study, nano-micelled curcumin was produced with natural sea salt with a view to comparing the in silico molecular binding affinity of pure curcumin compound to the active site of transthyretin. Using an optical light microscope and an electron microscope, it was found that the structure of the surface and the cross-section of nano-micelled curcumin was significantly different from natural sea salt. In particular, the crystal structure and nano-components in the nano-micelled curcumin were united, and the layer was more strongly stabilized than untreated salts. In the virtual 3D structure, in silico molecular docking study, the ligand binding affinity of nano-micelled curcumin to the transthyretin active site was found to be higher than that of pure curcumin. In addition, a nano-micelled curcumin formula interacted with more amino acid residues of transthyretin domains. The pharmacophore feature of the nano-micelled curcumin also showed more condensed and constrained features than normal curcumin. These results suggest that nano-micelled curcumin may effectively bind to and stabilize transthyretin, thereby regulating transthyretin-related physiological diseases. Collectively, the nano-micelled curcumin process suggests that normal curcumin can be modified more efficiently into the novel bio-functional chemical formula to stabilize the transthyretin structure. Therefore, the nano-micelled curcumin process can be applied to the field of the regulation of Alzheimer's disease.


Binding affinity;curcumin;in silico study;nano-micelling;transthyretin


  1. Chen, J., He, Z. M., Wang, F. L., Zhang, Z. S., Liu, X. Z., Zhai, D. D. and Chen, W. D. 2015. Curcumin and its promise as an anticancer drug: An analysis of its anticancer and antifungal effects in cancer and associated complications from invasive fungal infections. Eur. J. Pharmacol. 772, 33-42.
  2. Ciccone, L., Tepshi, L., Nencetti, S. and Stura, E. A. 2015. Transthyretin complexes with curcumin and bromo-estradiol: evaluation of solubilizing multicomponent mixtures. N. Biotechnol. 32, 54-64.
  3. Ferreira, N., Saraiva, M. J. and Almeida, M. R. 2011. Natural polyphenols inhibit different steps of the process of transthyretin (TTR) amyloid fibril formation. FEBS Lett. 585, 2424-2430.
  4. Husseinil, G. A., Kherbeckl, L., Pitt, W. G., Hubbell, J. A., Christensen, D. A. and Velluto, D. 2015. Kinetics of ultrasonic drug delivery from targeted micelles. J. Nanosci. Nanotechnol. 15, 2099-2104.
  5. Khanmohammadi, M., Elmizadeh, H. and Ghasemi, K. 2015. Investigation of size and morphology of chitosan nanoparticles used in drug delivery system employing chemometric technique. Iran. J. Pharm. Res. 14, 665-675.
  6. Kim, D. C. and Lee, C. E. 2013. NXCL-4950, a novel composite applicable to peripheral skin, is capable of increasing skin temperature by enhancing capillary circulation. Clin. Exp. Dermatol. 38, 244-250.
  7. Kittitheeranun, P., Sanchavanakit, N., Sajomsang, W. and Dubas, S. T. 2010. Loading of curcumin in polyelectrolyte multilayers. Langmuir 26, 6869-6873.
  8. Lu, Y. and Park, K. 2013. Polymeric micelles and alternative nanonized delivery vehicles for poorly soluble drugs. Int. J. Pharm. 453, 198-214.
  9. Masbuchin, A. N., Rohman, M. S., Putri, J. F., Cahyaningtyas, M. and Widodo. 2015. 279(Val-->Phe) Polymorphism of lipoprotein-associated phospholipase A2 resulted in changes of folding kinetics and recognition to substrate. Comput. Biol. Chem. 59 Pt A, 199-207.
  10. Mohan, M., James, P., Valsalan, R. and Nazeem, P. A. 2015. Molecular docking studies of phytochemicals from Phyllanthus niruri against Hepatitis B DNA Polymerase. Bioinformation 11, 426-431.
  11. Naksuriya, O., Okonogi, S., Schiffelers, R. M. and Hennink, W. E. 2014. Curcumin nanoformulations: a review of pharmaceutical properties and preclinical studies and clinical data related to cancer treatment. Biomaterials 35, 3365-3383.
  12. Pullakhandam, R., Srinivas, P. N., Nair, M. K. and Reddy, G. B. 2009. Binding and stabilization of transthyretin by curcumin. Arch. Biochem. Biophys. 485, 115-119.
  13. Rao, P. P., Mohamed, T., Teckwani, K. and Tin, G. 2015. Curcumin Binding to Beta Amyloid: A Computational Study. Chem. Biol. Drug. Des. 86, 813-820.
  14. Saelices, L., Johnson, L. M., Liang, W. Y., Sawaya, M. R., Cascio, D., Ruchala, P., Whitelegge, J., Jiang, L., Riek, R. and Eisenberg, D. S. 2015. Uncovering the Mechanism of Aggregation of Human Transthyretin. J. Biol. Chem. 290, 28932-28943.
  15. Sordillo, L. A., Sordillo, P. P. and Helson, L. 2015. Curcumin for the Treatment of Glioblastoma. Anticancer. Res. 35, 6373-6378.
  16. Blake, C. C., Geisow, M. J., Oatley, S. J., Rerat, B. and Rerat, C. 1978. Structure of prealbumin: secondary, tertiary and quaternary interactions determined by Fourier refinement at 1.8 A. J. Mol. Biol. 121, 339-356.
  17. Stein, T. D., Anders, N. J., DeCarli, C., Chan, S. L., Mattson, M. P. and Johnson, J. A. 2004. Neutralization of transthyretin reverses the neuroprotective effects of secreted amyloid precursor protein (APP) in APPSW mice resulting in tau phosphorylation and loss of hippocampal neurons: support for the amyloid hypothesis. J. Neurosci. 24, 7707-7717.
  18. Suh, W. H., Suslick, K. S., Stucky, G. D. and Suh, Y. H. 2009. Nanotechnology, nanotoxicology, and neuroscience. Prog. Neurobiol. 87, 133-170.
  19. Sunde, M., Richardson, S. J., Chang, L., Pettersson, T. M., Schreiber, G. and Blake, C. C. 1996. The crystal structure of transthyretin from chicken. Eur. J. Biochem. 236, 491-499.
  20. Tang, Y. P., Haslam, S. Z., Conrad, S. E. and Sisk, C. L. 2004. Estrogen increases brain expression of the mRNA encoding transthyretin, an amyloid beta scavenger protein. J. Alzheimers. Dis. 6, 413-420.
  21. Trott, O. and Olson, A. J. 2010. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem. 31, 455-461.
  22. Turnbull, E. R., Kaunda, K., Harris, J. B., Kapata, N., Muvwimi, M. W., Kruuner, A., Henostroza, G. and Reid, S. E. 2011. An evaluation of the performance and acceptability of three LED fluorescent microscopes in Zambia: lessons learnt for scale-up. PLoS. One. 6, e27125.
  23. Xia, H., Zhao, Y. and Tong, R. 2016. Ultrasound-mediated polymeric micelle drug delivery. Adv. Exp. Med. Biol. 880, 365-384.
  24. Yallapu, M. M., Ebeling, M. C., Chauhan, N., Jaggi, M. and Chauhan, S. C. 2011. Interaction of curcumin nanoformulations with human plasma proteins and erythrocytes. Int. J. Nanomedicine 6, 2779-2790.
  25. Yallapu, M. M., Nagesh, P. K., Jaggi, M. and Chauhan, S. C. 2015. Therapeutic applications of curcumin nanoformulations. AAPS J. 17, 1341-1356.
  26. Zheng, W., Lu, Y. M., Lu, G. Y., Zhao, Q., Cheung, O. and Blaner, W. S. 2001. Transthyretin, thyroxine, and retinol-binding protein in human cerebrospinal fluid: effect of lead exposure. Toxicol. Sci. 61, 107-114.
  27. Zheng, Z., Sun, Y., Liu, Z., Zhang, M., Li, C. and Cai, H. 2015. The effect of curcumin and its nanoformulation on adjuvant-induced arthritis in rats. Drug. Des. Devel. Ther. 9, 4931-4942.