Show simple item record

dc.creatorMoreno-Castillo E.
dc.creatorÁlvarez-Ginarte Y.M.
dc.creatorValdés-Tresanco M.E.
dc.creatorMontero-Cabrera L.A.
dc.creatorMoreno E.
dc.creatorValiente P.A.
dc.descriptionAlzheimer's disease is a progressive neurodegenerative disorder characterized by the abnormal processing of the Tau and the amyloid precursor proteins. The unusual aggregation of Tau is based on the formation of intermolecular ?-sheets through two motifs: 275VQIINK280 and 306VQIVYK311. Phenylthiazolyl-hydrazides (PTHs) are capable of inhibiting/disassembling Tau aggregates. However, the disaggregation mechanism of Tau oligomers by PTHs is still unknown. In this work, we studied the disruption of the oligomeric form of the Tau motif 306VQIVYK311 by PTHs through molecular docking, molecular dynamics, and free energy calculations. We predicted hydrophobic interactions as the major driving forces for the stabilization of Tau oligomer, with V306 and I308 being the major contributors. Nonpolar component of the binding free energy is essential to stabilize Tau-PTH complexes. PTHs disrupted mainly the van der Waals interactions between the monomers, leading to oligomer destabilization. Destabilization of full Tau filament by PTHs and emodin was not observed in the sampled 20 ns; however, in all cases, the nonpolar component of the binding free energy is essential for the formation of Tau filament-PTH and Tau filament-emodin. These results provide useful clues for the design of more effective Tau-aggregation inhibitors. © 2020 John Wiley & Sons Ltd
dc.publisherJohn Wiley and Sons Ltd
dc.sourceJournal of Molecular Recognition
dc.subjectmolecular docking
dc.subjectmolecular dynamics
dc.subjectTau protein
dc.titleUnderstanding the disrupting mechanism of the Tau aggregation motif 306VQIVYK311 by phenylthiazolyl-hydrazides inhibitors
dc.publisher.programFacultad de Ciencias Básicas
dc.publisher.facultyFacultad de Ciencias Básicas
dc.affiliationMoreno-Castillo, E., Faculty of Chemistry, University of Havana, La Habana, Cuba, Department of Molecular Signal Processing, Leibniz Institute of Plant Biochemistry, Halle (Saale), Germany; Álvarez-Ginarte, Y.M., Faculty of Chemistry, University of Havana, La Habana, Cuba; Valdés-Tresanco, M.E., Center of Protein Studies, Faculty of Biology, University of Havana, La Habana, Cuba, Department of Biological Sciences, University of Calgary, Calgary, AB, Canada; Montero-Cabrera, L.A., Faculty of Chemistry, University of Havana, La Habana, Cuba; Moreno, E., Faculty of Basic Sciences, Universidad de Medellín, Medellín, Colombia; Valiente, P.A., Center of Protein Studies, Faculty of Biology, University of Havana, La Habana, Cuba, Donnelly Centre for Cellular & Biomolecular Research University of Toronto, Toronto, ON, Canada
dc.relation.referencesSpillantini, M.G., Goedert, M., Tau protein pathology in neurodegenerative diseases (1998) Trends Neurosci, 21, pp. 428-433
dc.relation.referencesBraak, H., Braak, E., Demonstration of amyloid deposits and neurofibrillary changes in whole brain sections (1991) Brain Pathol, 1, pp. 213-216
dc.relation.referencesRyan, P., Patel, B., Makwana, V., Peptides, Peptidomimetics and carbohydrate-peptide conjugates as Amyloidogenic aggregation inhibitors for Alzheimer's disease (2018) ACS Chem Neurosci, 9, pp. 1530-1551
dc.relation.referencesWischik, C.M., Wischik, D.J., Storey, J.M.D., Harrington, C.R., (2010) Rationale for Tau-Aggregation Inhibitor Therapy in Alzheimer's Disease and Other Tauopathies. Vol. 1: Beta-Amyloid, Tau Protein and Glucose Metabolism, , Scotland, UK, Royal Society of Chemistry
dc.relation.referencesWilcock, G.K., Esiri, M.M., Plaques, tangles and dementia. A quantitative study (1982) J Neurol Sci, 56, pp. 343-356
dc.relation.referencesWeingarten, M.D., Lockwood, A.H., Hwo, S.Y., Kirschner, M.W., A protein factor essential for microtubule assembly (1975) Proc Natl Acad Sci U S A, 72, pp. 1858-1862
dc.relation.referencesvon Bergen, M., Friedhoff, P., Biernat, J., Heberle, J., Mandelkow, E.M., Mandelkow, E., Assembly of tau protein into Alzheimer paired helical filaments depends on a local sequence motif (306VQIVYK311) forming beta structure (2000) PNAS, 97 (10), pp. 5129-5134
dc.relation.referencesvon Bergen, M., Barghorn, S., Li, L., Mutations of tau protein in frontotemporal dementia promote aggregation of paired helical filaments by enhancing local beta structure (2001) J Biol Chem, 276, pp. 48165-48174
dc.relation.referencesWille, H., Drewes, G., Biernat, J., Mandelkow, E.M., Mandelkow, E., Alzheimer-like paired helical filaments and antiparallel dimers formed from microtubule-associated protein tau in vitro (1992) J Cell Biol, 118, pp. 573-584
dc.relation.referencesTaniguchi, S., Suzuki, N., Masuda, M., Inhibition of heparin-induced tau filament formation by Phenothiazines, polyphenols, and Porphyrins (2005) J Biol Chem, 280, pp. 7614-7623
dc.relation.referencesBulic, B., Pickhardt, M., Mandelkow, E.M., Mandelkow, E., Tau protein and tau aggregation inhibitors (2010) Neuropharmacology, 59, pp. 276-289
dc.relation.referencesHimmelstein, D.S., Ward, S.M., Lancia, J.K., Patterson, K.R., Binder, L.I., Tau as a therapeutic target in neurodegenerative disease (2012) Pharmacol Ther, 136 (1), pp. 8-22
dc.relation.referencesPickhardt, M., Larbig, G., Khlistunova, I., Phenylthiazolyl-Hydrazide and its derivatives are potent inhibitors of tau aggregation and toxicity in vitro and in cells (2007) Biochemistry, 46, pp. 10016-10023
dc.relation.referencesSong, M., Sun, Y., Luo, Y., Zhu, Y., Liu, Y., Li, H., Exploring the mechanism of inhibition of au nanoparticles on the aggregation of amyloid-?(16 22) peptides at the atom level by all-atom molecular dynamics (2018) Int J Mol Sci, 19 (6)
dc.relation.referencesSukumaran, S.D., Faraj, F.L., Lee, V.S., Othman, R., Bucklem, M.J.C., 2-Aryl-3-(arylideneamino)-1,2-dihydroquinazoline-4(3H)-ones as inhibitors of cholinesterases and self-induced b-amyloid (Ab)aggregation: biological evaluations and mechanistic insights from molecular dynamics simulations (2018) RSC Adv, 8, pp. 7818-7831
dc.relation.referencesTran, L., Ha-Duong, T., Exploring the Alzheimer amyloid-? peptide conformational ensemble: a review of molecular dynamics approaches (2015) Peptides, 69, pp. 86-91
dc.relation.referencesZhao, J.H., Liu, H.L., Chuang, C.K., Liu, K.T., Tsai, W.B., Ho, Y., Molecular dynamics simulations to investigate the stability and aggregation behaviour of the amyloid-forming peptide VQIVYK from Tau protein (2010) Mol Simul, 36 (13), pp. 1013-1024
dc.relation.referencesBerhanu, W.M., Masunov, A.E., Atomistic mechanism of polyphenol amyloid aggregation inhibitors: molecular dynamics study of Curcumin, Exifone, and Myricetin interaction with the segment of tau peptide oligomer (2014) J Biomol Struct Dyn, 33, pp. 1399-1411
dc.relation.referencesFitzpatrick, A.W.P., Falcon, B., He, S., Cryo-EM structures of tau filaments from Alzheimer's disease (2017) Nature, 547, pp. 185-190
dc.relation.referencesSeo, J.-H., Cha, E., Kim, H.-T., Multiply charged oligomer complexes composed of the amyloid-forming peptides NNQQNY, VQIVYK, and LYQLEN analyzed by collision-induced dissociation with electrospray ionization mass spectroscopy (2017) Int J Mass Spectrom, 415, pp. 55-62
dc.relation.referencesGoux, W.J., Kopplin, L., Nguyen, A.D., The formation of straight and twisted filaments from short tau peptides (2004) J Biol Chem, 279, pp. 26868-26875
dc.relation.referencesSawaya, M.R., Sambashivan, S., Nelson, R., Atomic structures of amyloid cross-beta spines reveal varied steric zippers (2007) Nature, 447, pp. 453-457
dc.relation.referencesKhlistunova, I., Biernat, J., Wang, Y., Inducible expression of tau repeat domain in cell models of Taupathy. Aggregation is toxic to cells but can be reversed by inhibitors drugs (2006) J Biol Chem, 281 (2), pp. 1205-1214
dc.relation.referencesWang, R., Lai, L., Wang, S., Further development and validation of empirical scoring functions for structure-based binding affinity prediction (2002) J Comput Aided Mol Des, 16, pp. 11-26
dc.relation.referencesHernandez Gonzalez, J.E., Hernandez Alvarez, L., Pascutti, P.G., Valiente, P.A., Predicting binding modes of reversible peptide-based inhibitors of falcipain-2 consistent with structure-activity relationships (2017) Proteins, 85, pp. 1666-1683
dc.relation.referencesStjernschantz, E., Oostenbrink, C., Improved ligand-protein binding affinity predictions using multiple binding modes (2010) Biophys J, 98, pp. 2682-2691
dc.relation.referencesThompson, D.C., Humblet, C., Joseph-McCarthy, D., Investigation of MM-PBSA rescoring of docking poses (2008) J Chem Inf Model, 48, pp. 1081-1091
dc.relation.referencesLindstrom, A., Edvinsson, L., Johansson, A., Postprocessing of docked protein-ligand complexes using implicit solvation models (2011) J Chem Inf Model, 51, pp. 267-282
dc.relation.referencesGuimaraes, C.R., Cardozo, M., MM-GB/SA rescoring of docking poses in structure-based lead optimization (2008) J Chem Inf Model, 48, pp. 958-970
dc.relation.referencesHou, T., Wang, J., Li, Y., Wang, W., Assessing the performance of the molecular mechanics/Poisson Boltzmann surface area and molecular mechanics/generalized born surface area methods. II the accuracy of ranking poses generated from docking (2011) J Comp Chem, 32, pp. 866-877
dc.relation.referencesRastelli, G., Del Rio, A., Degliesposti, G., Sgobba, M., Fast and accurate predictions of binding free energies using MM-PBSA and MM-GBSA (2010) J Comput Chem, 31, pp. 797-810
dc.relation.referencesSun, H., Li, Y., Tian, S., Xu, L., Hou, T., Assessing the performance of MM/PBSA and MM/GBSA methods. 4. Accuracies of MM/PBSA and MM/GBSA methodologies evaluated by various simulation protocols using PDBbind data set (2014) Phys Chem Chem Phys, 16, pp. 16719-16729
dc.relation.referencesNecula, M., Chirita, C.N., Kuret, J., Cyanine dye N744 inhibits tau fibrillization by blocking filament extension: implications for the treatment of Tauopathic neurodegenerative diseases (2005) Biochemistry, 44 (30), pp. 10227-10237
dc.relation.referencesChang, E., Congdon, E.E., Honson, N.S., Duff, K.E., Kuret, J., Structure-activity relationship of cyanine tau aggregation inhibitors (2009) J Med Chem, 52 (11), pp. 3539-3547
dc.relation.referencesPickhardt, M., Biernat, J., Khlistunova, I., N-Phenylamine derivatives as aggregation inhibitors in cell models of Tauopathy (2007) Curr Alzheimer Res, 4, pp. 397-402
dc.relation.referencesBulic, B., Pickhardt, M., Khlistunova, I., Rhodanine-based tau aggregation inhibitors in cell models of Tauopathy (2007) Angew Chem Int Ed, 46, pp. 9215-9219
dc.relation.referencesPickhardt, M., Gazova, Z., von Bergen, M., Anthraquinones inhibit tau aggregation and dissolve Alzheimer's paired helical filaments in vitro and in cells (2005) J Biol Chem, 280 (5), pp. 3628-3635
dc.relation.referencesCrowe, A., Huang, W., Ballatore, C., Identification of Aminothienopyridazine inhibitors of tau assembly by quantitative high-throughput screening (2009) Biochemistry, 48 (32), pp. 7732-7745
dc.relation.referencesMark, A.E., van Gunsteren, W.F., Decomposition of the free energy of a system in terms of specific interactions. Implications for theoretical and experimental studies (1994) J Mol Biol, 240 (2), pp. 167-176
dc.relation.referencesBissantz, C., Kuhn, B., Stahl, M., A medicinal chemist's guide to molecular interactions (2010) J Med Chem, 53 (14), pp. 5061-5084
dc.relation.referencesMiranda, W.E., Noskov, S.Y., Valiente, P.A., Improving the LIE method for binding free energy calculations of protein?ligand complexes (2015) J Chem Inf Model, 55, pp. 1867-1877
dc.relation.referencesÅqvist, J., Marelius, J., The linear interaction energy method for predicting ligand binding free energies (2001) Comb Chem High Throughput Screen, 4, pp. 613-626
dc.relation.referencesBjelic, S., Nervall, M., Gutiérrez-de-Terán, H., Ersmark, K., Hallberg, A., Åqvist, J., Computational inhibitor design against malaria plasmepsins (2007) CMLS, 64, pp. 2285-2305
dc.relation.referencesWang, C.K., Northfield, S.E., Huang, Y.-H., Ramos, M.C., Craik, D.J., Inhibition of tau aggregation using a naturally-occurring cyclic peptide scaffold (2016) Eur J Med Chem, 109, pp. 342-349
dc.relation.referencesSanner, M.F., Python: a programming language for software integration and development (1999) J Mol Graphics Mod, 17, pp. 57-61
dc.relation.referencesTrott, O., Olson, A.J., Software news and update AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading (2010) J Comput Chem, 31 (2), pp. 455-461
dc.relation.referencesPronk, S., Páll, S., Schulz, R., GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit (2013) Bioinformatics, 29, pp. 845-854
dc.relation.referencesHornak, V., Abel, R., Okur, A., Strockbine, B., Roitberg, A., Simmerling, C., Comparison of multiple Amber force-fields and development of improved protein backbone parameters (2006) Proteins, 65 (3), pp. 712-725
dc.relation.referencesWang, J.M., Wolf, R.M., Caldwell, J.W., Kollman, P.A., Development and testing of a General Amber force-field (2004) J Comput Chem, 25, pp. 1157-1174
dc.relation.referencesLindahl, E.R., Molecular dynamics simulations (2008) Molecular Modeling of Proteins, 443, pp. 1-24. , Kukol A, ed., Hertfordshire, UK, Humana Press
dc.relation.referencesCase, D.A., Babin, V., Berryman, J.T., (2014) AMBER 14, , San Francisco, CA, University of California

Files in this item


There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record