Computational Insights into β-Carboline Inhibition of Monoamine Oxidase A
Monoamine oxidases (MAOs) are an important group of enzymes involved in the degradation of neurotransmitters and their imbalanced mode of action may lead to the development of various neuropsychiatric or neurodegenerative disorders. In this work, we report the results of an in-depth computational st...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/19/6711 |
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| author | Alja Prah Tanja Gavranić Andrej Perdih Marija Sollner Dolenc Janez Mavri |
| author_facet | Alja Prah Tanja Gavranić Andrej Perdih Marija Sollner Dolenc Janez Mavri |
| author_sort | Alja Prah |
| collection | DOAJ |
| description | Monoamine oxidases (MAOs) are an important group of enzymes involved in the degradation of neurotransmitters and their imbalanced mode of action may lead to the development of various neuropsychiatric or neurodegenerative disorders. In this work, we report the results of an in-depth computational study in which we performed a static and a dynamic analysis of a series of substituted β-carboline natural products, found mainly in roasted coffee and tobacco smoke, that bind to the active site of the MAO-A isoform. By applying molecular docking in conjunction with structure-based pharmacophores and molecular dynamics simulations coupled with dynamic pharmacophores, we extensively investigated the geometric aspects of MAO-A binding. To gain insight into the energetics of binding, we used the linear interaction energy (LIE) method and determined the key anchors that allow productive β-carboline binding to MAO-A. The results presented herein could be applied in the rational structure-based design and optimization of β-carbolines towards preclinical candidates that would target the MAO-A enzyme and would be applicable especially in the treatment of mental disorders such as depression. |
| first_indexed | 2024-03-09T21:22:31Z |
| format | Article |
| id | doaj.art-2a87db7b198b4438b629519f5eab17fb |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T21:22:31Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-2a87db7b198b4438b629519f5eab17fb2023-11-23T21:15:59ZengMDPI AGMolecules1420-30492022-10-012719671110.3390/molecules27196711Computational Insights into β-Carboline Inhibition of Monoamine Oxidase AAlja Prah0Tanja Gavranić1Andrej Perdih2Marija Sollner Dolenc3Janez Mavri4National Institute of Chemistry, SI-1000 Ljubljana, SloveniaNational Institute of Chemistry, SI-1000 Ljubljana, SloveniaNational Institute of Chemistry, SI-1000 Ljubljana, SloveniaFaculty of Pharmacy, University of Ljubljana, SI-1000 Ljubljana, SloveniaNational Institute of Chemistry, SI-1000 Ljubljana, SloveniaMonoamine oxidases (MAOs) are an important group of enzymes involved in the degradation of neurotransmitters and their imbalanced mode of action may lead to the development of various neuropsychiatric or neurodegenerative disorders. In this work, we report the results of an in-depth computational study in which we performed a static and a dynamic analysis of a series of substituted β-carboline natural products, found mainly in roasted coffee and tobacco smoke, that bind to the active site of the MAO-A isoform. By applying molecular docking in conjunction with structure-based pharmacophores and molecular dynamics simulations coupled with dynamic pharmacophores, we extensively investigated the geometric aspects of MAO-A binding. To gain insight into the energetics of binding, we used the linear interaction energy (LIE) method and determined the key anchors that allow productive β-carboline binding to MAO-A. The results presented herein could be applied in the rational structure-based design and optimization of β-carbolines towards preclinical candidates that would target the MAO-A enzyme and would be applicable especially in the treatment of mental disorders such as depression.https://www.mdpi.com/1420-3049/27/19/6711monoamine oxidaseβ-carbolinesdepressionlinear interaction energy |
| spellingShingle | Alja Prah Tanja Gavranić Andrej Perdih Marija Sollner Dolenc Janez Mavri Computational Insights into β-Carboline Inhibition of Monoamine Oxidase A Molecules monoamine oxidase β-carbolines depression linear interaction energy |
| title | Computational Insights into β-Carboline Inhibition of Monoamine Oxidase A |
| title_full | Computational Insights into β-Carboline Inhibition of Monoamine Oxidase A |
| title_fullStr | Computational Insights into β-Carboline Inhibition of Monoamine Oxidase A |
| title_full_unstemmed | Computational Insights into β-Carboline Inhibition of Monoamine Oxidase A |
| title_short | Computational Insights into β-Carboline Inhibition of Monoamine Oxidase A |
| title_sort | computational insights into β carboline inhibition of monoamine oxidase a |
| topic | monoamine oxidase β-carbolines depression linear interaction energy |
| url | https://www.mdpi.com/1420-3049/27/19/6711 |
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