An In Silico Study for Expanding the Utility of Cannabidiol in Alzheimer’s Disease Therapeutic Development
Cannabidiol (CBD), a major non-psychoactive component of the cannabis plant, has shown therapeutic potential in Alzheimer’s disease (AD). In this study, we identified potential CBD targets associated with AD using a drug-target binding affinity prediction model and generated CBD analogs using a gene...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/21/16013 |
| _version_ | 1797631757303939072 |
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| author | Kyudam Choi Yurim Lee Cheongwon Kim |
| author_facet | Kyudam Choi Yurim Lee Cheongwon Kim |
| author_sort | Kyudam Choi |
| collection | DOAJ |
| description | Cannabidiol (CBD), a major non-psychoactive component of the cannabis plant, has shown therapeutic potential in Alzheimer’s disease (AD). In this study, we identified potential CBD targets associated with AD using a drug-target binding affinity prediction model and generated CBD analogs using a genetic algorithm combined with a molecular docking system. As a result, we identified six targets associated with AD: Endothelial NOS (ENOS), Myeloperoxidase (MPO), Apolipoprotein E (APOE), Amyloid-beta precursor protein (APP), Disintegrin and metalloproteinase domain-containing protein 10 (ADAM10), and Presenilin-1 (PSEN1). Furthermore, we generated CBD analogs for each target that optimize for all desired drug-likeness properties and physicochemical property filters, resulting in improved <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mi>p</mi><mi>I</mi><mi>C</mi><mn>50</mn></mrow></semantics></math></inline-formula> values and docking scores compared to CBD. Molecular dynamics (MD) simulations were applied to analyze each target’s CBD and highest-scoring CBD analogs. The MD simulations revealed that the complexes of ENOS, MPO, and ADAM10 with CBD exhibited high conformational stability, and the APP and PSEN1 complexes with CBD analogs demonstrated even higher conformational stability and lower interaction energy compared to APP and PSEN1 complexes with CBD. These findings demonstrated the capable binding of the six identified targets with CBD and the enhanced binding stability achieved with the developed CBD analogs for each target. |
| first_indexed | 2024-03-11T11:27:54Z |
| format | Article |
| id | doaj.art-e8ac9dedc9fc423c963cfb8427b645e3 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T11:27:54Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e8ac9dedc9fc423c963cfb8427b645e32023-11-10T15:06:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-11-0124211601310.3390/ijms242116013An In Silico Study for Expanding the Utility of Cannabidiol in Alzheimer’s Disease Therapeutic DevelopmentKyudam Choi0Yurim Lee1Cheongwon Kim2Heerae Co., Ltd., Seoul 06253, Republic of KoreaDepartment of Software, Sejong University, Seoul 05006, Republic of KoreaDepartment of Software, Sejong University, Seoul 05006, Republic of KoreaCannabidiol (CBD), a major non-psychoactive component of the cannabis plant, has shown therapeutic potential in Alzheimer’s disease (AD). In this study, we identified potential CBD targets associated with AD using a drug-target binding affinity prediction model and generated CBD analogs using a genetic algorithm combined with a molecular docking system. As a result, we identified six targets associated with AD: Endothelial NOS (ENOS), Myeloperoxidase (MPO), Apolipoprotein E (APOE), Amyloid-beta precursor protein (APP), Disintegrin and metalloproteinase domain-containing protein 10 (ADAM10), and Presenilin-1 (PSEN1). Furthermore, we generated CBD analogs for each target that optimize for all desired drug-likeness properties and physicochemical property filters, resulting in improved <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mi>p</mi><mi>I</mi><mi>C</mi><mn>50</mn></mrow></semantics></math></inline-formula> values and docking scores compared to CBD. Molecular dynamics (MD) simulations were applied to analyze each target’s CBD and highest-scoring CBD analogs. The MD simulations revealed that the complexes of ENOS, MPO, and ADAM10 with CBD exhibited high conformational stability, and the APP and PSEN1 complexes with CBD analogs demonstrated even higher conformational stability and lower interaction energy compared to APP and PSEN1 complexes with CBD. These findings demonstrated the capable binding of the six identified targets with CBD and the enhanced binding stability achieved with the developed CBD analogs for each target.https://www.mdpi.com/1422-0067/24/21/16013cannabidiolAlzheimer’s diseasetarget identificationdrug optimizationmolecular dockingmolecular dynamics |
| spellingShingle | Kyudam Choi Yurim Lee Cheongwon Kim An In Silico Study for Expanding the Utility of Cannabidiol in Alzheimer’s Disease Therapeutic Development International Journal of Molecular Sciences cannabidiol Alzheimer’s disease target identification drug optimization molecular docking molecular dynamics |
| title | An In Silico Study for Expanding the Utility of Cannabidiol in Alzheimer’s Disease Therapeutic Development |
| title_full | An In Silico Study for Expanding the Utility of Cannabidiol in Alzheimer’s Disease Therapeutic Development |
| title_fullStr | An In Silico Study for Expanding the Utility of Cannabidiol in Alzheimer’s Disease Therapeutic Development |
| title_full_unstemmed | An In Silico Study for Expanding the Utility of Cannabidiol in Alzheimer’s Disease Therapeutic Development |
| title_short | An In Silico Study for Expanding the Utility of Cannabidiol in Alzheimer’s Disease Therapeutic Development |
| title_sort | in silico study for expanding the utility of cannabidiol in alzheimer s disease therapeutic development |
| topic | cannabidiol Alzheimer’s disease target identification drug optimization molecular docking molecular dynamics |
| url | https://www.mdpi.com/1422-0067/24/21/16013 |
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