Virtual screening, molecular docking, molecular dynamics, and MM-GBSA approaches identify prospective fructose-1,6-bisphosphatase inhibitors from pineapple for diabetes management
Diabetes affects millions globally and poses treatment challenges. Targeting the enzyme fructose-1,6-bisphosphatase (FBPase) in gluconeogenesis and exploring plant-based therapies offer potential solutions for improving diabetes management while supporting sustainability and medicinal advancements....
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| Format: | Article |
| Language: | English English |
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Taylor & Francis
2023
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| Online Access: | http://umpir.ump.edu.my/id/eprint/40547/2/Hossain%20et%20al.%202023.%20Virtual%20screening%20molecular%20docking%20molecular%20dynamics%20and%20MM-GBSA%20approaches%20identify%20prospective%20fructose-1%206-bisphosphatase%20inhibitors%20from%20pine.pdf http://umpir.ump.edu.my/id/eprint/40547/3/Virtual%20screening%20molecular%20docking%20molecular%20dynamics%20and%20MM-GBSA%20approaches%20identify%20prospective%20fructose-1%206-bisphosphatase%20inhibitors%20from%20pine.pdf |
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| author | Hossain, Md. Sanower Roney, Miah Mohd Yusri, Mohd Yunus Jun Haslinda, Shariffuddin |
| author_facet | Hossain, Md. Sanower Roney, Miah Mohd Yusri, Mohd Yunus Jun Haslinda, Shariffuddin |
| author_sort | Hossain, Md. Sanower |
| collection | UMP |
| description | Diabetes affects millions globally and poses treatment challenges. Targeting the enzyme fructose-1,6-bisphosphatase (FBPase) in gluconeogenesis and exploring plant-based therapies offer potential solutions for improving diabetes management while supporting sustainability and medicinal advancements. Utilizing pineapple (Ananas comosus L. Merr.) waste as a source of drug precursors could be valuable for health and environmental care due to its medicinal benefits and abundant yearly biomass production. Therefore, this study conducted a virtual screening to identify potential natural compounds from pineapple that could inhibit FBPase activity. A total of 112 compounds were screened for drug-likeness and ADMET properties, and molecular docking simulations were performed on 20 selected compounds using blind docking. The lead compound, butane-2,3-diyl diacetate, was subjected to 100 ns MD simulations, revealing a binding energy of −5.4 kcal/mol comparable to metformin (−5.6 kcal/mol). The MD simulation also confirmed stable complexes with crucial hydrogen bonds. Glu20, Ala24, Thr27, Gly28, Glu29, Leu30, Val160, Met177, Asp178, and Cys179 were identified as key amino acids that stabilized the human liver FBPase-butane-2,3-diyl diacetate complex, while Tyr215 and Asp218 played a crucial role in the human liver FBPase-Metformin complex. Our study indicates that the lead compound has high intestinal solubility. Therefore, it would show rapid bloodstream distribution and effective action on the target protein, making butane-2,3-diyl diacetate a potential antidiabetic drug candidate. However, further investigations in vitro, preclinical, and clinical trials are required to thoroughly assess its efficacy and safety. |
| first_indexed | 2024-03-06T13:14:11Z |
| format | Article |
| id | UMPir40547 |
| institution | Universiti Malaysia Pahang |
| language | English English |
| last_indexed | 2024-03-06T13:14:11Z |
| publishDate | 2023 |
| publisher | Taylor & Francis |
| record_format | dspace |
| spelling | UMPir405472024-02-29T06:26:43Z http://umpir.ump.edu.my/id/eprint/40547/ Virtual screening, molecular docking, molecular dynamics, and MM-GBSA approaches identify prospective fructose-1,6-bisphosphatase inhibitors from pineapple for diabetes management Hossain, Md. Sanower Roney, Miah Mohd Yusri, Mohd Yunus Jun Haslinda, Shariffuddin HD28 Management. Industrial Management TP Chemical technology Diabetes affects millions globally and poses treatment challenges. Targeting the enzyme fructose-1,6-bisphosphatase (FBPase) in gluconeogenesis and exploring plant-based therapies offer potential solutions for improving diabetes management while supporting sustainability and medicinal advancements. Utilizing pineapple (Ananas comosus L. Merr.) waste as a source of drug precursors could be valuable for health and environmental care due to its medicinal benefits and abundant yearly biomass production. Therefore, this study conducted a virtual screening to identify potential natural compounds from pineapple that could inhibit FBPase activity. A total of 112 compounds were screened for drug-likeness and ADMET properties, and molecular docking simulations were performed on 20 selected compounds using blind docking. The lead compound, butane-2,3-diyl diacetate, was subjected to 100 ns MD simulations, revealing a binding energy of −5.4 kcal/mol comparable to metformin (−5.6 kcal/mol). The MD simulation also confirmed stable complexes with crucial hydrogen bonds. Glu20, Ala24, Thr27, Gly28, Glu29, Leu30, Val160, Met177, Asp178, and Cys179 were identified as key amino acids that stabilized the human liver FBPase-butane-2,3-diyl diacetate complex, while Tyr215 and Asp218 played a crucial role in the human liver FBPase-Metformin complex. Our study indicates that the lead compound has high intestinal solubility. Therefore, it would show rapid bloodstream distribution and effective action on the target protein, making butane-2,3-diyl diacetate a potential antidiabetic drug candidate. However, further investigations in vitro, preclinical, and clinical trials are required to thoroughly assess its efficacy and safety. Taylor & Francis 2023 Article PeerReviewed pdf en http://umpir.ump.edu.my/id/eprint/40547/2/Hossain%20et%20al.%202023.%20Virtual%20screening%20molecular%20docking%20molecular%20dynamics%20and%20MM-GBSA%20approaches%20identify%20prospective%20fructose-1%206-bisphosphatase%20inhibitors%20from%20pine.pdf pdf en http://umpir.ump.edu.my/id/eprint/40547/3/Virtual%20screening%20molecular%20docking%20molecular%20dynamics%20and%20MM-GBSA%20approaches%20identify%20prospective%20fructose-1%206-bisphosphatase%20inhibitors%20from%20pine.pdf Hossain, Md. Sanower and Roney, Miah and Mohd Yusri, Mohd Yunus and Jun Haslinda, Shariffuddin (2023) Virtual screening, molecular docking, molecular dynamics, and MM-GBSA approaches identify prospective fructose-1,6-bisphosphatase inhibitors from pineapple for diabetes management. Journal of Biomolecular Structure and Dynamics. ISSN 0739-1102. (In Press / Online First) (In Press / Online First) https://doi.org/10.1080/07391102.2023.2276889 10.1080/07391102.2023.2276889 |
| spellingShingle | HD28 Management. Industrial Management TP Chemical technology Hossain, Md. Sanower Roney, Miah Mohd Yusri, Mohd Yunus Jun Haslinda, Shariffuddin Virtual screening, molecular docking, molecular dynamics, and MM-GBSA approaches identify prospective fructose-1,6-bisphosphatase inhibitors from pineapple for diabetes management |
| title | Virtual screening, molecular docking, molecular dynamics, and MM-GBSA approaches identify prospective fructose-1,6-bisphosphatase inhibitors from pineapple for diabetes management |
| title_full | Virtual screening, molecular docking, molecular dynamics, and MM-GBSA approaches identify prospective fructose-1,6-bisphosphatase inhibitors from pineapple for diabetes management |
| title_fullStr | Virtual screening, molecular docking, molecular dynamics, and MM-GBSA approaches identify prospective fructose-1,6-bisphosphatase inhibitors from pineapple for diabetes management |
| title_full_unstemmed | Virtual screening, molecular docking, molecular dynamics, and MM-GBSA approaches identify prospective fructose-1,6-bisphosphatase inhibitors from pineapple for diabetes management |
| title_short | Virtual screening, molecular docking, molecular dynamics, and MM-GBSA approaches identify prospective fructose-1,6-bisphosphatase inhibitors from pineapple for diabetes management |
| title_sort | virtual screening molecular docking molecular dynamics and mm gbsa approaches identify prospective fructose 1 6 bisphosphatase inhibitors from pineapple for diabetes management |
| topic | HD28 Management. Industrial Management TP Chemical technology |
| url | http://umpir.ump.edu.my/id/eprint/40547/2/Hossain%20et%20al.%202023.%20Virtual%20screening%20molecular%20docking%20molecular%20dynamics%20and%20MM-GBSA%20approaches%20identify%20prospective%20fructose-1%206-bisphosphatase%20inhibitors%20from%20pine.pdf http://umpir.ump.edu.my/id/eprint/40547/3/Virtual%20screening%20molecular%20docking%20molecular%20dynamics%20and%20MM-GBSA%20approaches%20identify%20prospective%20fructose-1%206-bisphosphatase%20inhibitors%20from%20pine.pdf |
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