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Biological conscious behavior is associated with human brain activity and inactivity which can be understood by conscious mind studies. Human brain and conscious mind studies have a correlation with microtubules, therefore, these studies are done on the basis of microtubules alignment, their association with other proteins and formulation. Protein conformation dynamics (regulated by quantum mechanical van der Waals London forces) are responsible for the activities in living cells. Quantum Hopfield network model of the brain explains five levels of neural interaction for learning and association . Microtubules having diameter of 25 nanometers comprises to be the largest cytoskeleton filament. Alpha and beta tubulin are the two subunits of microtubules, forms a heterodimer. The present work focuses on the topology of Microtubule Associated Proteins (MAPs) and tubulin protein. The study also includes the understanding of interaction of tubulin with MAP-tau and Anti-Tau with the help of I-Tasser and PyMOL methods separately. Models of MAPs with C-Score < -1.5 is considered to be the most acceptable model. PyMol study helped in constructing a 3D structure of tubulin protein and its interaction with Tau and Anti-Tau and thereby, helped in visualizing the binding site or preference of interaction at specific position of protein. Memory, learning and information processing are interrelated and microtubules/tubulin plays a key role in all these processes. Tau aggregation is linked to neurodegeneration and clinical manifestations of Alzheimer's Disease, a memory loss disease. PyMOL study showed strong interaction of tubulin with Anti-Tau, an antibody. This antibody against tau can prevent the trans-synaptic transmission of tau between neurons and hence memory (information processing) can be regained.
Fleming JP, Gong H, Rose DG. Secondary structure determines protein topology. Protein Science. 2006;1829–1834.
Hameroff S, Nip A, Porter M, Tuszynski J. Conduction pathways in microtubules, biological quantum computation, and consciousness. BioSystems. 2002;64:149–168.
Hameroff S, Penrose R. Orchestrated reduction coherence in brain microtubules: The “Orch OR” model for consciousness. Cognitive Science. 2007;31:1035-1045.
Cang Z. A topological approach for protein classification. Mol. Based Math. Biol. 2015;3:140- 162.
Martin ACR. The ups and downs of protein topology; rapid comparison of protein structure. Oxford University Press. 2000;13:829–837.
Taylor WR, Aszodi A. A book on Protein geometry, classification, topology and symmetry- A computational analysis of structure. Taylor & Francis; 2005.
Vazquez A. Global protein function prediction from protein-protein interaction network. Nat Biotechnol. 2003;21:697-700.
Glazer DS, Radmer JR. Improving Structure-Based Function Prediction Using Molecular Dynamics. Cell. 2009;15:919-929.
Von Heijne G. Membrane-protein topology. Nature. 2006;7:909-919.
Sharan R, Ideker T. Modeling cellular machinery through biological network comparison. Nature Biotechnology. 2006;24:427-433.
Yook SH, Oltvai ZN, Barabaski AL. Functional and topological characterization of protein interaction networks. Proteomics. 2004;4:928-942.
Torrance GM, Gilbert DR, Michalopoulos I, Westhead DW. Protein structure topological comparison, discovery and matching service. Oxford University Press. 2005;21:2537–2538.
Ponstingl H, Krauhs E, Little M, Kempf T, Warbinek R, Ade W. Complete amino acid sequence of f8-tubulin from porcine brain. Nature. 1981;78:4156-4160.
Ponstingl H, Krauhs E, Little M, Kempf T. Complete amino acid sequence of a-tubulin from porcine brain. Nature. 1981;78:2757-2761.
Levitt M, Warshell A. Computer stimulation of protein folding. Nature. 1975;253:694-698.
Skolnick J. Computational studies of protein folding. Bioengineering and Biophysics, Computing in Science and Engineering; 2001.
Aung Z, Tan KL. Rapid 3D protein structure database searching using information retrieval techniques. Advance Access publication. 2004;20:1045–1052.
Murzin AG, Brenner SE, Hubbard T, Chotia C. SCOP; a structural classification of protein database for the investigation of sequences and structure. J. Mol. Biol. 1995;4:536-540.
Johnson M, Zaretskaya I, Raytselis Y, Merezhuk Y, McGinnis S, Madden TL. Ncbi blast: a better web interface. Nucleic acids research. 2008;36 (suppl 2):270- 275.
Cowley A, Li W, Uludag W, Gur T, McWilliam H, Squizzato S, Park YM, Buso N, Lopez R. The embl- ebi bioinformatics web and programmatic tools framework. Nucleic acids research. 2015;279.
Madhusudhan MS, Sali A. Comparative Protein Structure Modeling. Current Protocols in Bioinformatics. 2006;5:1-30.
Kim H. et al.: The periodic association of MAP2 with brain microtubules in vitro. J. Cell Biol. 1979;80: 266-276.
Iwata M, Muneoka KT, Shirayama Y, Yamamoto A, Kawahora R. A study of a dendritic marker, microtubule-associated protein-2 (MAP-2), in rats neonatally treated neurosteroids, pregnenolone and dehyroepiendrosterone (DHEA). Neurosc. Lett. 2005;386 (3):145-149.
Cummings J. Anti- Tau Trials for Alzheimer’s Disease: A Report From The EU/US/CTAD Task Force. The J. Prevention of Alzheimer’s disease; 2019.
Barbier P, Zejneli O, Martinho M, Lasora A, Belle V, Smet-Nocca C, Tsvetkov PO, Devred F, Landrieu I. Role of Tau as a Microtubule-Associated Protein: Structural and Functional Aspects. Front. Aging Neurosci. 2009;11, Article 204.
Roy A, Kucukural A, Zhang Y. I-TASSER: a unified platform for automated protein structure and function prediction. Nature Protocols. 2010;5:725-738.
Zhang Y. I – TASSER server for protein 3D structure predictions. BMC Bioinformatics. 9, Article number. 2008;40.
Zhou H, Robert A, Skolnick F. Ab Initio Protein Structure Prediction Using Chunk-TASSER. Biophy. J. 2007;97:1510–1518.
Zhou H. TASSER based CASP7 protein structure prediction. Biophy. J. 2007;90-97.
Dehmelt L, Halpain S: The MAP2/Tau family of microtubule-associated proteins. Genome Biol. 2005;6 (1):204.
Sahni P, Bhanupriya, Shreya, Jaya: Tubulin Conformation and Anaesthetic Interaction - An Experimental Study. Biochem Anal Biochem. 2016;5:1.
Sahni P, Kumar M, Pachauri R. Mechanism of Propofol's Action on MAP Rich Tubulin and Actin - An In Vitro Study. Biochem Anal Biochem. 2017;6 (3):1-7.
Sahni Pushpa, Jessy D. Priscilla: A study on change in conformation of tubulin on interacting with propofol via Time of Flight Mass Spectrometry. International Journal of Pharmaceutical, Chemical and Biological Sciences (IJPCBS). 2019;9(3):123-127. ISSN: 2249-9504.
Zhang Y, Sali A, Ludena RF, Skolnick. Scoring Function for Automated Assessment of Protein Structure Template Quality, The Structure, Function, and Bioinformatics. 2004;57:702–710.
Sahni Pushpa, Chemistry of Microtubules and Consciousness, Lambert Academic Publishing, Germany; 2013, ISBN 978-3659315121.
Jordan M, Wilson L. Modulation of Microtubule Dynamics by Tau in Living Cells, Implications for Development and Neurodegeneration. J. Mol. Biol. 2004;23:2720–2728.
Morris M, Maeda S, Vossel K, Mucke L. The many faces of tau. Neuron. 2011;70:410- 426.
Guo T, Noble W, Hanger DP. Roles of tau protein in health and disease. Acta Neuropathol. 2017;133:665- 704.
Kihara D, Skolnick J. The PDB is a covering set of small protein structures. J. Mol. Biol. 2003;334:793–80.
Faber J, Portugal R, Rosa PL. Information processing in brain microtubules. BioSystems. 2006;83:1–9.
Hameroff S. Quantum computation in brain microtubules? The Penrose–Hameroff‘ Orch OR’ model of consciousness. R. Soc. Lond. 1998;356:1869–1896.
Hameroff SR. The Brain Is Both Neurocomputer and Quantum Computer. Science. 2007;31:1035–1045.