332
Views
24
CrossRef citations to date
0
Altmetric
Research Articles

Understanding the conformational flexibility and electrostatic properties of curcumin in the active site of rhAChE via molecular docking, molecular dynamics, and charge density analysis

, &
Pages 3627-3647 | Received 26 Apr 2016, Accepted 07 Nov 2016, Published online: 04 Jan 2017

References

  • Andrew, J., & Ben, L. (2011). Adaptive stochastic methods for sampling driven molecular systems. The Journal of Chemical Physics, 135, 084125 (11 pages).
  • Arlan, S. G., França, T. C. C., Figueroa-Villar, J. D., & Pascutti, P. G. (2011). Molecular dynamics simulations and QM/MM studies of the reactivation by 2-PAM of Tabun inhibited human acethylcolinesterase. Journal of the Brazilian Chemical Society, 22, 155–165.
  • Arlan, S. G., Françab, T. C. C., & Osmair, V. O. (2016). Computational studies of acetylcholinesterase complexed with fullerene derivatives: A new insight for Alzheimer disease treatment. Journal of Biomolecular Structure and Dynamics, 34, 1307–1316.
  • Babitha, K. V., Shanmuga Sundaram, R., Annapandian, V. M., Abhirama, B. R., Sudha, M., Thiyagarajan, T., … Pushpa, S. (2014). Natural products and its derived drugs for the treatment of neurodegenerative disorders: Alzheimer’s disease – A review. British Biomedical Bulletin, 2, 359–370.
  • Bader, R. F. W. (1994). Atoms in molecules: A quantum theory, International series of monographs in chemistry 22. Oxford: Oxford University Press.
  • Bader, R. F. W., Tal, Y., Anderson, S. G., & Nguyen-Dang, T. T. (1980). Quantum topology: Theory of molecular structure and its change. Israel Journal of Chemistry, 19, 8–29.10.1002/ijch.v19:1-4
  • Bai, D. (2007). Development of huperzine A and B for treatment of Alzheimer’s disease. Pure and Applied Chemistry, 79, 469–479.
  • Balasubramanian, K. (2006). Molecular orbital basis for yellow curry spice curcumin’s prevention of Alzheimer’s DISEASE. Journal of Agricultural and Food Chemistry, 54, 3512–3520.10.1021/jf0603533
  • Bartolucci, C., Perola, E., Pilger, C., Fels, G., & Lamba, D. (2001). Three dimensional structure of a complex of galanthamine (Nivalin) with Acetylinesterase from “Torpedo californica”: Implications for the design of new anti- Alzheimer drugs. Proteins: Structure, Function, and Genetics, 42, 182–191.10.1002/(ISSN)1097-0134
  • Bartus, R. T., Dean, R. L., Beer, B., & Lippa, A. S. (1982). The cholinergic hypothesis of geriatric memory dysfunction. Science, 217, 408–414.10.1126/science.7046051
  • Berendsen, H. J. C., Postma, J. P. M., van Gunsteren, W. F., DiNola, A., & Haak, J. R. (1984). Molecular dynamics with coupling to an external bath. The Journal of Chemical Physics, 81, 3684–3690.10.1063/1.448118
  • Brian, J. B., Sebnem, G. E., Edmond, Y. L., Fattebert, J. C., Emigh, A., & Lightstone, F. C. (2015). Wrench in the works of human acetylcholinesterase: Soman induced conformational changes revealed by molecular dynamics simulations. PLoS ONE, 10, 1–31.
  • Brooijmans, N., & Kuntz, I. D. (2003). Molecular recognition and docking algorithms. Annual Review of Biophysics and Biomolecular Structure, 32, 335–373.10.1146/annurev.biophys.32.110601.142532
  • Case, D. A., Babin, V., Berryman, J. T., Betz, R. M., Cai, Q., Cerutti, D. S., … Kollman, P. A. (2014). AMBER 14. San Francisco: University of California.
  • Chandrabhan, S., Ghulam, J. K., & Kuldeep, U. (2014). Identification of potential herbal inhibitor of acetylcholinesterase associated Alzheimer’s disorders using molecular docking and molecular dynamics simulation. Biochemistry Research International, 2014, Article ID 705451, 7 p.
  • Cheeseman, J., Keith, T. A., & Bader, R. F. W. (1992). AIMPAC program package. Hamilton: McMaster University.
  • Chopra, K., Misra, S., & Kuhad, A. (2011). Current perspectives on pharmacotherapy of Alzheimer’s disease. Expert Opinion on Pharmacotherapy, 12, 335–350.10.1517/14656566.2011.520702
  • Chunying, N., Yechun, X., Yong, X., Xiaomin, L., Wenhu, D., Israel, S., … Jiang, H. (2005). Dynamic mechanism of E2020 binding to acetylcholinesterase: A steered molecular dynamics simulation. The Journal of Physical Chemistry B, 109, 23730–23738.
  • Daniel, M. Q. (1987). Acetylcholinesterase: Enzyme structure, reaction dynamics, and virtual transition states. Chemical Reviews, 87, 955–979.
  • Daniel, R. R., & Cheatham, T. E. (2013). PTRAJ and CPPTRAJ: Software for processing and analysis of molecular dynamics trajectory data. Journal of Chemical Theory and Computation, 9, 3084–3095.
  • DeLano, W. L. (2002). PyMol molecular graphics system. San Carlos, CA: DeLano Scientific.
  • Devipriya, B., & Kumaradhas, P. (2013). Molecular flexibility and the electrostatic moments of curcumin and its derivatives in the active site of p300: A theoretical charge density study. Chemico-Biological Interactions, 204, 153–165.10.1016/j.cbi.2013.05.002
  • Dittrich, B., & Matta, F. C. (2014). Contributions of charge-density research to medicinal chemistry. International Union of Crystallography, 1, 457–469.10.1107/S2052252514018867
  • Dvir, H., Jiang, H. L., Wong, D. M., Harel, M., Chetrit, M., He, X. C., … Sussman, L. (2002). X-ray structures of Torpedo californica acetylcholinesterase complexed with (+)-huperzine A and (–)-huperzine B: structural evidence for an active site rearrangement. Biochemistry, 41, 10810–10818.10.1021/bi020151+
  • Dyall, G. K., & Knut, F. (2007). Introduction to relativistic quantum chemistry. Oxford: Oxford University Press.
  • Eickerling, G., Mastalerz, R., Herz, V., Scherer, W., Himmel, H., & Reiher, M. (2007). Relativistic effects on the topology of the electron density. Journal of Chemical Theory and Computation, 3, 2182–2197.10.1021/ct7001573
  • Elizabeth, B., & Ursula, R. (2015). Mixed quantum mechanical/molecular mechanical molecular dynamics simulations of biological systems in ground and electronically excited states. Chemical Reviews, 115, 6217–6263.
  • Esatbeyoglu, T., Huebbe, P., Ernst, I. M. A., Chin, D., Wagner, A. E., & Rimbach, G. (2012). Curcumin-from molecule to biological function. Angewandte Chemie International Edition, 51, 5308–5332.10.1002/anie.201107724
  • Fischer, F. C. (1987). General Hartree–Fock program. Computer Physics Communications, 43, 355–365.10.1016/0010-4655(87)90053-1
  • Friesner, R. A., Banks, J. L., Murphy, R. B., Halgren, T. A., Klicic, J. J., Mainz, D. T., … Shenkin, P. S. (2004). Glide: A new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. Journal of Medicinal Chemistry, 47, 1739–1749.10.1021/jm0306430
  • Friesner, R. A., Murphy, R. B., Repasky, M. P., Frye, L. L., Greenwood, J. R., Halgren, T. A., … Mainz, D. T. (2006). Extra precision glide: Docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. Journal of Medicinal Chemistry, 49, 6177–6196.10.1021/jm051256o
  • Frisch, M. J., Trucks, G. W., Schlegel, H. B., Scuseria, G. E., Robb, M. A., Cheeseman, J. R., … Pople, J. A. (2005). Gaussian 03, Revision D.1. Wallingford, CT: Gaussian Inc.
  • Fukui, K. (1982). Role of frontier orbitals in chemical reactions. Science, 218, 747–754.10.1126/science.218.4574.747
  • Fusheng, Y., Giselle, P. L., Aynun, N. B., Oliver, J. U., Mychica, R. S., Surendra, S. A., … Gregory, M. C. (2005). Curcumin inhibits formation of amyloid β oligomers and fibrils, binds plaques, and reduces amyloid in vivo. The Journal of Biological Chemistry, 280, 5892–5901.
  • Gatti, C., & Macchi, P. (2012). Modern charge-density analysis. New York, NY: Springer.10.1007/978-90-481-3836-4
  • Gharaghani, S., Khayamian, T., & Ebrahimi, M. (2013). Molecular dynamics simulation study and molecular docking descriptors in structure-based QSAR on acetylcholinesterase (AChE) inhibitors. SAR and QSAR in Environmental Research, 24, 773–794.10.1080/1062936X.2013.792877
  • Girija, C. R., Begum, N. S., Syed, A. A., & Thiruvenkatam, V. (2004). Hydrogen-bonding and C–H∙∙∙π interactions in 1,7-bis (4-hydroxy-3-methoxyphenyl) heptane-3,5-dione (tetrahydrocurcumin). Acta Crystallographica, C60, o611–o613.
  • Gitay, K., Michal, H., Kurt, G., Lilly, T., Baruch, V., Arie, L., … Joel, L. S. (2000). Structures of recombinant native and E202Q mutant human acetylcholinesterase complexed with the snake-venom toxin fasciculin-II. Acta Crystallographica D, 56, 1385–1394.
  • Glenn, J. M., & Adam, H. (1999). Molecular dynamics algorithms for path integrals at constant pressure. The Journal of Chemical Physics, 110, 7 pages.
  • Glide. (2014). Small-molecular drug discovery suite 2014-2, Glide, version 6.3. New York, NY: Schrodinger, LLC.
  • Hanne, H. T., Jan, K., & Arvid, M. (1982). Structural studies of curcuminoids. I. The crystal structure of curcumin. Acta Chemica Scandinavica, B36, 475–479.
  • Hay, D., Israel, S., Michal, H., Terrone, L. R., & Joel, L. S. (2010). Acetylcholinesterase: From 3D structure to function. Chemico-Biological Interactions, 187, 10–22.
  • Humphrey, W., Dalke, A., & Schulten, K. (1996). VMD: Visual molecular dynamics. Journal of Molecular Graphics, 14, 33–38.10.1016/0263-7855(96)00018-5
  • Hyun, A. J., Byung-Sun, M., Takako, Y., Je-Hyun, L., Yeong, S. K., & Choi, J. S. (2009). Anti-Alzheimer and antioxidant activites of coptidis rhizome alkaloids. Biological &/and Pharmaceutical Bulletin, 32, 1433–1438.
  • Imbimbo, P. B., Lombard, J., & Pomara, N. (2005). Pathophysiology of Alzheimer’s disease. Neuroimaging Clinics of North America, 15, 727–753.10.1016/j.nic.2005.09.009
  • Indra, P. I. (2013). Chemical and structural features influencing the biological activity of curcumin. Current Pharmaceutical Design, 19, 2093–2100.
  • Induced Fit docking protocol. (2014). Small-molecular drug discovery suite 2014-2, version 6.3. New York, NY: Schrodinger, LLC
  • Jacobson, S. A., & Sabbagh, M. N. (2008). Donepezil: Potential neuroprotective and disease-modifying effects. Expert Opinion on Drug Metabolism & Toxicology, 4, 1363–1369.10.1517/17425255.4.10.1363
  • James, A. M., Carmenza, M., Koushik, K., Lauren, W., Kevin, H., & Carlos, S. (2015). ff14SB: Improving the accuracy of protein side chain and backbone parameters from ff99SB. Journal of Chemical Theory and Computation, 11, 3696–3713.
  • Jean-paul, R., Giovanni, C., & Herman, B. J. C. (1977). Numerical integration of the Cartesian equations of motion of a system with constraints: Molecular dynamics of n-alkanes. Journal of Computational Physics, 23, 321–341.
  • Jesudason, E. P., Sridhar, S. K., Malar, E. J., Shanmugapandiyan, P., Inayathullah, M., Arul, V., … Jayakumar, R. (2009). Synthesis, pharmacological screening, quantum chemical and in vitro permeability studies of N-Mannich bases of benzimidazoles through bovine cornea. European Journal of Medicinal Chemistry, 44, 2307–2312.10.1016/j.ejmech.2008.03.043
  • Jiri, W., Zdenek, K., Kamil, K., Daniel, J., & Jaroslav, K. (2007). Acetylcholinesterase – The structural similarities and differences. Journal of Enzyme Inhibition and Medicinal Chemistry, 22, 417–424.
  • Jonah, C., Michael, J. R., Fiana, B., Michael, S. C., Ebony, N. G., James, L., … Jude, J. H. (2012). Structures of human Acetylcholinesterase in complex with pharmacologically important ligands. Journal of Medicinal Chemistry, 55, 10282–10286.
  • Jorgensen, W. L., Maxwell, D. S., & Tirado-Rives, J. (1996). Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids. Journal of the American Chemical Society, 118, 11225–11236.10.1021/ja9621760
  • Kaihsu, T., Tongye, S., Richard, H. H., Yves, B., Pascale, M., & McCammon, J. A. (2002). Mechanism of acetylcholinesterase inhibition by fasciculin: A 5-ns molecular dynamics simulation. Journal of the American Chemical Society, 124, 6153–6161.
  • Kaihsu, T., Tongye, S., Rjesson, S., Marios, P., & McCammon, J. A. (2001). Analysis of a 10-ns molecular dynamics simulation of mouse acetylcholinesterase. Biophysical Journal, 81, 715–724.
  • Kitchen, D. B., Decornez, H., Furr, J. R., & Bajorath, J. (2004). Docking and scoring in virtual screening for drug discovery: Methods and applications. Nature Reviews Drug Discovery, 3, 935–949.10.1038/nrd1549
  • Kolev, T. M., Velcheva, E. A., Stamboliyska, B. A., & Spiteller, M. (2005). DFT and experimental studies of the structure and vibrational spectra of curcumin. International Journal of Quantum Chemistry, 102, 1069–1079.10.1002/(ISSN)1097-461X
  • Koritsanszky, T. S., & Coppens, P. (2001). Chemical applications of X-ray charge-density analysis. Chemical Reviews, 101, 1583–1628.10.1021/cr990112c
  • Koritsanszky, T., Macchi, P., Gatti, C., Farrugia, L. J., Mallinson, P. R., Volkov, A., & Richter, T. (2007). XD-2006. A computer program package for multipole refinement and topological analysis of charge densities and evaluation of intermolecular energies from experimental or theoretical structure factors. Version 5.33. Glasgow: University of Glasgow.
  • Koritsanszky, T., Richter, T., Gatti, P. C., Howard, S., Mallinson, P. R., Farrugia, L. J., … Hansen, N. K. (2003). XD – A computer program package for multipole refinement and analysis of electron densities from diffraction data. Berlin: Freie Universit¨at Berlin.
  • Labanowski, J. K., & Andzelm, J. W. (1991). Density functional methods in chemistry. New York, NY: Springer.10.1007/978-1-4612-3136-3
  • Lee, W. H., Loo, C. Y., Bebawy, M., Luk, F., Mason, R. S., & Rohanizadeh, R. (2013). Curcumin and its derivatives: Their application in neuropharmacology and neuroscience in the 21st century. Current Neuropharmacology, 11, 338–378.10.2174/1570159X11311040002
  • Leech, A. R. (1996). Molecular modelling principles and applications. Essex: Addison Wesley Longman.
  • Lesley, J. S., & Karen, L. G. (2000). Galantamine – A review of its use in Alzheimer’s disease. Drugs, 60, 1095–1122.
  • LigPrep. (2014). Schrödinger release 2014-2: LigPrep, version 3.0. New York, NY: Schrödinger, LLC.
  • Madhavi Sastry, G., Adzhigirey, M., Day, T., Annabhimoju, R., & Sherman, W. (2013). Protein and ligand preparation: Parameters, protocols, and influence on virtual screening enrichments. Journal of Computer-Aided Molecular Design, 27, 221–234.10.1007/s10822-013-9644-8
  • Maestro. (2014). Schrodinger release 2014-2, Maestro, version 9.8. New York, NY: Schrödinger, LLC.
  • Mague, J. T., Alworth, W. L., & Payton, F. L. (2004). Curcumin and derivatives. Acta Crystallographica, C60, o608–o610.
  • Manjinder, S., Maninder, K., Hitesh, K., Rajan, C., & Om, S. (2013). Acetylcholinesterase inhibitors as Alzheimer therapy: From nerve toxins to neuroprotection. European Journal of Medicinal Chemistry, 70, 165–188.
  • Manolova, Y., Deneva, V., Antonov, L., Drakalska, E., Momekova, D., & Lambov, N. (2014). The effect of the water on the curcumin tautomerism: A quantitative approach. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 132, 815–820.10.1016/j.saa.2014.05.096
  • Mark, E. T., & Glenn, J. M. (2000). Understanding modern molecular dynamics: Techniques and applications. The Journal of Physical Chemistry B, 104, 159–178.
  • Martin, K., & McCommon, J. A. (2002). Molecular dynamics simulation of biomolecules. Nature Structural & Molecular Biology, 9, 646–652.
  • Matta, C. F., Boyd, R. J., & Becke, A. (2007). The quantum theory of atoms in molecules. Weinheim: Wiley-VCH Verlag GmbH & Co. KGaA.10.1002/9783527610709
  • Matthew, P. J., David, L. P., Chaya, S. R., Tyler, J. F. D., Barry, H., David, E. S., … Friesner, A. (2004). Hierarchical approach to all-atom protein loop prediction. Proteins: Structure, Function, and Bioinformatics, 55, 351–367.
  • Menon, V. P., & Sudheer, A. R. (2007). Antioxidant and anti-inflammatory properties of curcumin. Advances in Experimental Medicine and Biology, 595, 105–125.10.1007/978-0-387-46401-5
  • Michael, F. H., & Barbara, D. (2014). Structure and dynamics of TIP3P, TIP4P, and TIP5P water near smooth and atomistic walls of different hydroaffinity. The Journal of Chemical Physics, 140, 174501.
  • Michael, R., Ravi, A., Ana, C. S., Serge, G., Yves, A., & Peter, D. B. (1999). Efficacy and safety of rivastigmine in patients with Alzheimer’s disease: International randomized controlled trial. BMJ, 318, 633–640.
  • Michal, H., Kryger, G., Terrone, L. R., William, D. M., Terence, L., Rodney, J. F., … Joel, L. S. (2000). Three-dimensional structures of Drosophila melanogaster acetylcholinesterase and of its complexes with two potent inhibitors. Protein Science, 9, 1063–1072.
  • Mishra, S., & Palanivelu, K. (2008). The effect of curcumin (turmeric) on Alzheimer’s disease: An overview. Annals of Indian Academy of Neurology, 11, 13–19.10.4103/0972-2327.40220
  • Mohammadi, K., Thompson, K. H., Patrick, B. O., Storr, T., Martins, C., Polishchuk, E., … Orvig, C. J. (2005). Synthesis and characterization of dual function vanadyl, gallium and indium curcumin complexes for medicinal applications. Journal of Inorganic Biochemistry, 99, 2217–2225.10.1016/j.jinorgbio.2005.08.001
  • Mona, M., Abdu, A., & Marwan, S. (2012). New acetylcholinesterase inhibitors for Alzheimer’s disease. International Journal of Alzheimer's Disease, 2012, Article ID 728983, 8 p.
  • Mulliken, R. S. (1955). Electronic population analysis on LCAO[single bond]MO molecular wave functions. I. The Journal of Chemical Physics, 23, 1833–1840.10.1063/1.1740588
  • Murray, A. P., Faraoni, M., Castro, M., Alza, N., & Cavallaro, V. (2013). Natural AChE inhibitors from plants and their contribution to Alzheimer’s disease therapy. Current Neuropharmacology, 11, 388–413.10.2174/1570159X11311040004
  • Narandra, S., Pandey, B. R., & Pankaj, V. (2011). An overview of phytotherapeutic approach in prevention and treatment of Alzhemer’s syndrome and dementia. International Journal of Pharmaceutical Science and Drug Research, 3, 162–172.
  • Nasimul, H., Huma, N., Ehtesham, J., Ashutosh, S., Sharmistha, D., Imtaiyaz, M. D., … Jayaram, B. (2015). Curcumin specifically binds to the human calcium-calmodulin-dependent protein kinase IV: Fluorescence and molecular dynamics simulation studies. Journal of Biomolecular Structure & Dynamics, 34, 572–574.
  • Oliveira, B. G., Pereira, F. S., de Araújo, R. C. M. U., & Ramos, M. N. (2006). The hydrogen bond strength: New proposals to evaluate the intermolecular interaction using DFT calculations and the AIM theory. Chemical Physics Letters, 427, 181–184.10.1016/j.cplett.2006.06.019
  • Pandey, A., Gupta, R. K., & Srivastava, R. (2011). Curcumin-the yellow magic. Asian J. Appl. Sci., 4, 343–354.
  • Parihar, M. S., & Hemnani, T. (2004). Alzheimer’s disease pathogenesis and therapeutic interventions. Journal of Clinical Neuroscience, 11, 456–467.10.1016/j.jocn.2003.12.007
  • Parimita, S. P., Suresh, S., & Guru Row, T. N. (2007). Redetermination of curcumin: (1E, 4Z, 6E)-5- hydroxy-1, 7- bis (4- hydroxy-3-methoxy-phenyl) hepta-1, 4, 6-trien-3-one. Acta Crystallographica, E63, o860–o862.
  • Parr, R. G., & Yang, W. (1989). Density functional theory of atoms and molecules. Oxford: Springer Netherlands.
  • Pekka, M., & Lennart, N. (2001). Structure and dynamics of the TIP3P, SPC, and SPC/E water models at 298 K. Journal of Physical Chemistry A, 105, 9954–9960.
  • Politzer, P., Murray, J. S., & Peralta-Inga, Z. (2001). Molecular surface electrostatic potentials in relation to noncovalent interactions in biological systems. International Journal of Quantum Chemistry, 85, 676–684.10.1002/(ISSN)1097-461X
  • Popelier, P. L. A. (2000). On the full topology of the Laplacian of the electron density. Coordination Chemistry Reviews, 197, 169–189.10.1016/S0010-8545(99)00189-7
  • Prime. (2014). Schrodinger release, 2014-2, Prime, version 3.6. New York, NY: Schrodinger, LLC.
  • QM-Polarized Ligand Docking. (2014). Small-molecular drug discovery suite 2014-2. version 6.3. New York, NY: Schrodinger, LLC.
  • Reed, A. E., Weinstock, R. B., & Weinhold, F. A. (1985). Natural population analysis. The Journal of Chemical Physics, 83, 735–746.10.1063/1.449486
  • Renuga Parameswari, A., Rajalakshmi, G., & Kumaradhas, P. (2015). A combined molecular docking and charge density analysis is a new approach for medicinal research to understand drug–receptor interaction: Curcumin–AChE model. Chemico-Biological Interactions, 225, 21–31.10.1016/j.cbi.2014.09.011
  • Scarpini, E., Schelterns, P., & Feldman, H. (2003). Treatment of Alzheimer’s disease: Current status and new perspectives. The Lancet Neurology, 2, 539–547.10.1016/S1474-4422(03)00502-7
  • Seifollah, J., & Marzieh, S. (2015). Study of curcumin behavior in two different lipid bilayer models of liposomal curcumin using molecular dynamics simulation. Journal of Biomolecular Structure & Dynamics, 34, 327–340.
  • Sherman, W., Day, T., Jacobson, M. P., Friesner, R. A., & Farid, R. (2006). Novel procedure for modeling ligand/receptor induced fit effects. Journal of Medicinal Chemistry, 49, 534–553.10.1021/jm050540c
  • Singh, A. K., Gupta, A., Mishra, A. K., Gupta, V., Bansal, P., & Kumar, S. (2010). Medicinal plant for curing Alzheimer’s disease. International Journal of Pharma and Bio Sciences, 1, 108–114.
  • Sinnokrot, M. O., Valeev, E. F., & Sherrill, C. D. (2002). Estimates of the ab initio limit for π−π interactions: The benzene dimer. Journal of the American Chemical Society, 124, 10887–10893.10.1021/ja025896h
  • Smith, S. J., & Sutcliffe, B. T. (1997). The development of computational chemistry in the United Kingdom. Reviews in Computational Chemistry, 10, 271–316.
  • Son, T. N., & Mai, S. L. (2013). Top-leads from natural products for treatment of Alzheimer’s disease: Docking and molecular dynamics study. Molecular Simulation, 39, 279–291.
  • Stanislaw, T. W., Terry, W. C., Ridgway, S. L., & McCammon, J. A. (1997). Molecular dynamics of acetylcholinesterase dimer complexed with tacrine. Journal of the American Chemical Society, 119, 9513–9522.
  • Stash, A. I., & Tsirelson, V. G. (2014). Developing WinXPRO: A software for determination of the multipole-model-based properties of crystals. Journal of Applied Crystallography, 47, 2086–2089.10.1107/S1600576714021566
  • Stefano, D. A. (2013). Plant-derived acetylcholinesterase inhibitory alkaloids for the treatment of Alzheimer’s disease. Botanics: Targets and Therapy, 3, 19–28.
  • Sugunadevi, S., & Lee, K. W. (2012). Pharmacophore-based virtual screening and density functional theory approach to identifying novel butyrylcholinesterase inhibitors. Acta Pharmacologica Sinica, 33, 964–978.
  • Sunil Kumar, T., & Singh, Sanjeev Kumar (2014). Insights into the structural basis of 3,5-diaminoindazoles as CDK2 inhibitors: Prediction of binding modes and potency by QM–MM interaction, MESP and MD simulation. Molecular BioSystems, 10, 2189–2201.
  • Tello-Franco, V., Lozada-Garcia, M. C., & Soriano-Garcia, M. (2013). Experimental and computational studies on the inhibition of acetylcholinesterase by curcumin and some of its derivatives. Current CADD, 9, 289–298.
  • Thimmappa, S. A., & Reddy, P. H. (2005). Can herbs provide a new generation of drugs for treating Alzheimer’s disease? Brain Research Reviews, 50, 361–376.
  • Thomas, A. H. (2009). Identifying and characterizing binding sites and assessing druggability. Journal of Chemical Information and Modeling, 49, 377–389.
  • Tongye, S., Kaihsu, T., Richard, H. H., & McCammon, J. A. (2002). Molecular dynamics of acetylcholinesterase. Accounts of Chemical Research, 2002, 332–340.
  • Tumiatti, V., Minarini, A., Bolognesi, M. L., Milelli, A., Rosini, M., & Melchiorre, C. (2010). Tacrine derivatives and Alzheimers disease. Current Medicinal Chemistry, 17, 1825–1838.10.2174/092986710791111206
  • Wang, B. S., Wang, H., Wei, Z. H., Song, Y. Y., Zhang, L., & Chen, H. Z. (2009). Efficacy and safety of natural acetylcholinesterase inhibitor huperzine A in the treatment of Alzheimer’s disease: An updated meta-analysis. Journal of Neural Transmission, 116, 457–465.10.1007/s00702-009-0189-x
  • Wilson, I. B., & Bergmann, F. (1950). Acetylcholinesterase: Dissociation constants of the active site groups. Journal of Biological Chemistry, 8, 683–692.
  • Workalemahu, M. B., & Artem, E. M. (2014). Atomistic mechanism of polyphenol amyloid aggregation inhibitors: Molecular dynamics study of curcumin, exifone, and myricetin interaction with the segment of tau peptide oligomer. Journal of Biomolecular Structure & Dynamics, 33, 1399–1411.
  • Yves, B., Jacques, G., Pierre, E. B., & Pascale, M. (1999). Conformational flexibility of the acetylcholinesterase tetramer suggested by X-ray crystallography. Journal of Biological Chemistry, 274, 30370–30376.
  • Yves, B., Palmer, T., Zoran, R., & Pascale, M. (2003). Structural insights into ligand interactions at the acetylcholinesterase peripheral anionic site. The EMBO Journal, 22, 1–12.
  • Zheng, Y., Zheng, M., Ling, X., Liu, Y., Xue, Y., An, L., … Jin, M. (2013). Design, synthesis, quantum chemical studies and biological activity evaluation of pyrazole-benzimidazole derivatives as potent Aurora A/B kinase inhibitors. Bioorganic & Medicinal Chemistry Letters, 23, 3523–3530.10.1016/j.bmcl.2013.04.039

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.