Proposed molecular mechanism of non-competitive inhibition using molecular dynamics simulations between α-glucosidase enzyme and mangostin compound as antidiabetic
Context: Further understanding of the molecular mechanisms is necessary since it is important for designing new drugs. This study aimed to understand the molecular mechanisms involved in the design of drugs that are inhibitors of the α-glucosidase enzyme. This research aims to gain further understan...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Springer
2024
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| Online Access: | http://psasir.upm.edu.my/id/eprint/118875/ http://psasir.upm.edu.my/id/eprint/118875/1/118875.pdf |
| _version_ | 1848867811157344256 |
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| author | Maulana, Ahmad Fariz Maksum, Iman Permana Sriwidodo, Sriwidodo Rukayadi, Yaya |
| author_facet | Maulana, Ahmad Fariz Maksum, Iman Permana Sriwidodo, Sriwidodo Rukayadi, Yaya |
| author_sort | Maulana, Ahmad Fariz |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | Context: Further understanding of the molecular mechanisms is necessary since it is important for designing new drugs. This study aimed to understand the molecular mechanisms involved in the design of drugs that are inhibitors of the α-glucosidase enzyme. This research aims to gain further understanding of the molecular mechanisms underlying antidiabetic drug design. The molecular docking process yielded 4 compounds with the best affinity energy, including γ-Mangostin, 1,6-dimethyl-ester-3-isomangostin, 1,3,6-trimethyl-ester-α-mangostin, and 3,6,7-trimethyl-ester-γ-mangostin. Free energy calculation with molecular mechanics with generalized born and surface area solvation indicated that the 3,6,7-trimethyl-γ-mangostin had a better free energy value compared to acarbose and simulated maltose together with 3,6,7-trimethyl-γ-mangostin compound. Based on the analysis of electrostatic, van der Waals, and intermolecular hydrogen interactions, 3,6,7-trimethyl-γ-mangostin adopts a noncompetitive inhibition mechanism, whereas acarbose adopts a competitive inhibition mechanism. Consequently, 3,6,7-trimethyl-ester-γ-mangostin, which is a derivative of γ-mangostin, can provide better activity in silico with molecular docking approaches and molecular dynamics simulations. Method: This research commenced with retrieving protein structures from the RCSB database, generating the formation of ligands using the ChemDraw Professional software, conducting molecular docking with the Autodock Vina software, and performing molecular dynamics simulations using the Amber software, along with the evaluation of RMSD values and intermolecular hydrogen bonds. Free energy, electrostatic interactions, and Van der Waals interaction were calculated using MM/GBSA. Acarbose, used as a positive control, and maltose are simulated together with test compound that has the best free energy. The forcefields used for molecular dynamics simulations are ff19SB, gaff2, and tip3p. |
| first_indexed | 2025-11-15T14:42:25Z |
| format | Article |
| id | upm-118875 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T14:42:25Z |
| publishDate | 2024 |
| publisher | Springer |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-1188752025-08-05T08:49:16Z http://psasir.upm.edu.my/id/eprint/118875/ Proposed molecular mechanism of non-competitive inhibition using molecular dynamics simulations between α-glucosidase enzyme and mangostin compound as antidiabetic Maulana, Ahmad Fariz Maksum, Iman Permana Sriwidodo, Sriwidodo Rukayadi, Yaya Context: Further understanding of the molecular mechanisms is necessary since it is important for designing new drugs. This study aimed to understand the molecular mechanisms involved in the design of drugs that are inhibitors of the α-glucosidase enzyme. This research aims to gain further understanding of the molecular mechanisms underlying antidiabetic drug design. The molecular docking process yielded 4 compounds with the best affinity energy, including γ-Mangostin, 1,6-dimethyl-ester-3-isomangostin, 1,3,6-trimethyl-ester-α-mangostin, and 3,6,7-trimethyl-ester-γ-mangostin. Free energy calculation with molecular mechanics with generalized born and surface area solvation indicated that the 3,6,7-trimethyl-γ-mangostin had a better free energy value compared to acarbose and simulated maltose together with 3,6,7-trimethyl-γ-mangostin compound. Based on the analysis of electrostatic, van der Waals, and intermolecular hydrogen interactions, 3,6,7-trimethyl-γ-mangostin adopts a noncompetitive inhibition mechanism, whereas acarbose adopts a competitive inhibition mechanism. Consequently, 3,6,7-trimethyl-ester-γ-mangostin, which is a derivative of γ-mangostin, can provide better activity in silico with molecular docking approaches and molecular dynamics simulations. Method: This research commenced with retrieving protein structures from the RCSB database, generating the formation of ligands using the ChemDraw Professional software, conducting molecular docking with the Autodock Vina software, and performing molecular dynamics simulations using the Amber software, along with the evaluation of RMSD values and intermolecular hydrogen bonds. Free energy, electrostatic interactions, and Van der Waals interaction were calculated using MM/GBSA. Acarbose, used as a positive control, and maltose are simulated together with test compound that has the best free energy. The forcefields used for molecular dynamics simulations are ff19SB, gaff2, and tip3p. Springer 2024 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/118875/1/118875.pdf Maulana, Ahmad Fariz and Maksum, Iman Permana and Sriwidodo, Sriwidodo and Rukayadi, Yaya (2024) Proposed molecular mechanism of non-competitive inhibition using molecular dynamics simulations between α-glucosidase enzyme and mangostin compound as antidiabetic. Journal of Molecular Modeling, 30 (5). art. no. 136. pp. 1-12. ISSN 1610-2940; eISSN: 0948-5023 https://link.springer.com/article/10.1007/s00894-024-05934-z?error=cookies_not_supported&code=4fa1718a-8c7c-4787-9eda-f0bba39ae339 10.1007/s00894-024-05934-z |
| spellingShingle | Maulana, Ahmad Fariz Maksum, Iman Permana Sriwidodo, Sriwidodo Rukayadi, Yaya Proposed molecular mechanism of non-competitive inhibition using molecular dynamics simulations between α-glucosidase enzyme and mangostin compound as antidiabetic |
| title | Proposed molecular mechanism of non-competitive inhibition using molecular dynamics simulations between α-glucosidase enzyme and mangostin compound as antidiabetic |
| title_full | Proposed molecular mechanism of non-competitive inhibition using molecular dynamics simulations between α-glucosidase enzyme and mangostin compound as antidiabetic |
| title_fullStr | Proposed molecular mechanism of non-competitive inhibition using molecular dynamics simulations between α-glucosidase enzyme and mangostin compound as antidiabetic |
| title_full_unstemmed | Proposed molecular mechanism of non-competitive inhibition using molecular dynamics simulations between α-glucosidase enzyme and mangostin compound as antidiabetic |
| title_short | Proposed molecular mechanism of non-competitive inhibition using molecular dynamics simulations between α-glucosidase enzyme and mangostin compound as antidiabetic |
| title_sort | proposed molecular mechanism of non-competitive inhibition using molecular dynamics simulations between α-glucosidase enzyme and mangostin compound as antidiabetic |
| url | http://psasir.upm.edu.my/id/eprint/118875/ http://psasir.upm.edu.my/id/eprint/118875/ http://psasir.upm.edu.my/id/eprint/118875/ http://psasir.upm.edu.my/id/eprint/118875/1/118875.pdf |