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In silico study of tacrine and acetylcholine binding profile with human acetylcholinesterase: docking and electronic structure

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Abstract

Alzheimer disease (AD) is a neurodegenerative process, one of the most common and incident dementia in the population over 60 years. AD manifests the presence of complex biochemical processes involved in neuronal degeneration, such as the formation of senile plaques containing amyloid-β peptides, the development of intracellular neurofibrillary tangles, and the suppression of the acetylcholine neurotransmitter. In this way, we performed a set of theoretical tests of tacrine ligand and acetylcholine neurotransmitter against the human acetylcholinesterase enzyme. Molecular docking was used to understand the most important interactions of these molecules with the enzyme. Computational chemistry calculation was carried out using MP2, DFT, and semi-empirical methods, starting from molecular docking structures. We have also performed studies regarding the non-covalent interactions, electron localization function, molecular electrostatic potential and explicit water molecule influence. For Trp86 residue, we show two main interactions in accordance to the results of the literature for TcAChE. First, intermolecular interactions of the cation-π and sigma-π type were found. Second, close stacking interactions were stablished between THA+ and Trp86 residue on one side and with Tyr337 residue on the other side.

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Acknowledgements

The authors acknowledge the computational resource of Laboratory of Computational Chemistry (LQC) of the University of Brasilia.

Funding

This work was supported by the Brazilian National Council for Scientific and Technological Development (CNPq 310071/2018–6, João B. L. Martins), Fundação de Apoio a Pesquisa do Distrito Federal (FAPDF 00193–00000229/2021–21, João B. L. Martins).

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  1. Computational Chemistry Laboratory, Institute of Chemistry, University of Brasilia, Brasilia, DF, 70910-900, Brazil

    Letícia A. Nascimento, Érica C. M. Nascimento & João B. L. Martins

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  2. Érica C. M. Nascimento
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Contributions

Letícia A. Nascimento: investigation, calculations, writing—original draft. Érica C. M. Nascimento: conceptualization, methodology, formal analysis, methodology. João B. L. Martins: conceptualization, formal analysis, methodology, resources, supervision, writing—review and editing.

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Correspondence to João B. L. Martins.

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Nascimento, L.A., Nascimento, É.C.M. & Martins, J.B.L. In silico study of tacrine and acetylcholine binding profile with human acetylcholinesterase: docking and electronic structure. J Mol Model 28, 252 (2022). https://doi.org/10.1007/s00894-022-05252-2

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