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Targeting imidazoline site on monoamine oxidase B through molecular docking simulations

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Abstract

Monoamine oxidase (MAO) is an enzyme of major importance in neurochemistry, because it catalyzes the inactivation pathway for the catecholamine neurotransmitters, noradrenaline, adrenaline and dopamine. In the last decade it was demonstrated that imidazoline derivatives were able to inhibit MAO activity. Furthermore, crystallographic studies identified the imidazoline-binding domain on monoamine oxidase B (MAO-B), which opens the possibility of molecular docking studies focused on this binding site. The goal of the present study is to identify new potential inhibitors for MAO-B. In addition, we are also interested in establishing a fast and reliable computation methodology to pave the way for future molecular docking simulations focused on the imidazoline-binding site of this enzyme. We used the program ‘molegro virtual docker’ (MVD) in all simulations described here. All results indicate that simplex evolution algorithm is able to succesfully simulate the protein-ligand interactions for MAO-B. In addition, a scoring function implemented in the program MVD presents high correlation coefficient with experimental activity of MAO-B inhibitors. Taken together, our results identified a new family of potential MAO-B inhibitors and mapped important residues for intermolecular interactions between this enzyme and ligands.

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Abbreviations

PD:

Parkinson's disease

IMAO:

Inhibitor of monoamine oxidase

MAO:

Monoamine oxidase

MAO-A:

Monoamine oxidase A

MAO-B:

Monoamine Oxidase B

FAD:

Flavin –adenine - dinucleotide

VS:

Virtual screening

2-BFI:

2-(2-benzofuranyl)-2-imidazoline

RMSD:

Root mean square deviation

PDB:

Protein data bank

EA:

Evolutionary algorithm

PLP:

Piecewise linear potencial

E intermol:

Energia intermolecular

E intramol:

energia intramolecular

RO5:

Lipinski’s rule of five

ρ:

Coeficiente de Spearman

IUPAC:

International Union of Pure and Applied Chemistry

IC50 :

Half maximal inhibitory concentration

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Acknowledgments

This work was supported by grants from the National Council for Scientific and Technological Development of Brazil (CNPq) and Instituto Nacional de Ciência e Tecnologia do Conselho Nacional de Desenvolvimento Científico e Tecnológico-Ministério de Ciência e Tecnologia (INCT-Tuberculose, CNPq-MCT, Brazil). WFA is senior researcher for CNPq (Brazil). The fellowship from CNPq-Brazil is also acknowledged (FPM).

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Authors and Affiliations

  1. Faculdade de Biociências, Laboratório de Bioquímica Estrutural (LaBioQuest), Pontifícia Universidade Católica do Rio Grande do Sul, (PUCRS), Av. Ipiranga 6681, Porto Alegre, RS, 90619-900, Brazil

    Fernanda Pretto Moraes & Walter Filgueira de Azevedo Jr

  2. Programa de Pós-Graduação em Medicina e Ciências da Saúde, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil

    Fernanda Pretto Moraes & Walter Filgueira de Azevedo Jr

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  1. Fernanda Pretto Moraes
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  2. Walter Filgueira de Azevedo Jr
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Correspondence to Walter Filgueira de Azevedo Jr.

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Moraes, F.P., de Azevedo, W.F. Targeting imidazoline site on monoamine oxidase B through molecular docking simulations. J Mol Model 18, 3877–3886 (2012). https://doi.org/10.1007/s00894-012-1390-7

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  • DOI: https://doi.org/10.1007/s00894-012-1390-7

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