Academic Journal
Tocotrienol as a multi-target inhibitor of ICAM-1, VCAM-1, and E-selectin: Comparison using AutoDock and GNINA docking with molecular dynamics simulation.
| Τίτλος: | Tocotrienol as a multi-target inhibitor of ICAM-1, VCAM-1, and E-selectin: Comparison using AutoDock and GNINA docking with molecular dynamics simulation. |
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| Συγγραφείς: | Abdah HW; Cardiovascular Advancement and Research Excellence Institute (CARE Institute), Universiti Teknologi MARA (UiTM) Sungai Buloh Selangor Campus, Sungai Buloh, Selangor 47000, Malaysia., Jusoh SA; Department of Life Science, Faculty of Pharmacy, Universiti Teknologi MARA (UiTM) Puncak Alam Selangor Campus, Puncak Alam, Selangor 42300, Malaysia., Dzulkharnien NSF; Cardiovascular Advancement and Research Excellence Institute (CARE Institute), Universiti Teknologi MARA (UiTM) Sungai Buloh Selangor Campus, Sungai Buloh, Selangor 47000, Malaysia., Hanafi NI; Cardiovascular Advancement and Research Excellence Institute (CARE Institute), Universiti Teknologi MARA (UiTM) Sungai Buloh Selangor Campus, Sungai Buloh, Selangor 47000, Malaysia., Mohd Nasir AM; Department of Life Science, Faculty of Pharmacy, Universiti Teknologi MARA (UiTM) Puncak Alam Selangor Campus, Puncak Alam, Selangor 42300, Malaysia., Abd Muid S; Cardiovascular Advancement and Research Excellence Institute (CARE Institute), Universiti Teknologi MARA (UiTM) Sungai Buloh Selangor Campus, Sungai Buloh, Selangor 47000, Malaysia; Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Universiti Teknologi MARA (UiTM) Sungai Buloh Selangor Campus, Sungai Buloh, Selangor 47000, Malaysia., Mohd Kasim NA; Cardiovascular Advancement and Research Excellence Institute (CARE Institute), Universiti Teknologi MARA (UiTM) Sungai Buloh Selangor Campus, Sungai Buloh, Selangor 47000, Malaysia; Department of Pathology, Faculty of Medicine, Universiti Teknologi MARA (UiTM) Sungai Buloh Selangor Campus, Sungai Buloh, Selangor 47000, Malaysia. Electronic address: noor202@uitm.edu.my. |
| Πηγή: | Computational biology and chemistry [Comput Biol Chem] 2026 Oct; Vol. 124 (Pt 1), pp. 109136. Date of Electronic Publication: 2026 May 27. |
| Τύπος έκδοσης: | Journal Article; Comparative Study |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Country of Publication: England NLM ID: 101157394 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-928X (Electronic) Linking ISSN: 14769271 NLM ISO Abbreviation: Comput Biol Chem Subsets: MEDLINE |
| Imprint Name(s): | Publication: Oxford : Elsevier Original Publication: Oxford : Pergamon, c2003- |
| Ιατρικοί όροι (MeSH): | Intercellular Adhesion Molecule-1*/metabolism , Intercellular Adhesion Molecule-1*/chemistry , Tocotrienols*/chemistry , Tocotrienols*/pharmacology , E-Selectin*/antagonists & inhibitors , E-Selectin*/metabolism , E-Selectin*/chemistry , Vascular Cell Adhesion Molecule-1*/antagonists & inhibitors , Vascular Cell Adhesion Molecule-1*/metabolism , Vascular Cell Adhesion Molecule-1*/chemistry , Molecular Dynamics Simulation* , Molecular Docking Simulation*, Humans |
| Περίληψη: | Atherosclerosis is a chronic inflammatory disease characterized by endothelial dysfunction and leukocyte adhesion, mediated by cell adhesion molecules such as E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1). Tocotrienols, a subgroup of vitamin E, exhibit potent antioxidant and anti-inflammatory properties, suggesting their potential role in attenuating atherosclerosis. This study comparatively evaluated the binding affinities and molecular interaction profiles of α-, β-, γ-, and δ tocotrienol isomers towards E-selectin, ICAM-1, and VCAM-1 using molecular docking approaches, followed by molecular dynamic simulation to assess the stability of the top-ranked protein-ligand complexes. The docking experiment was conducted using MolModa, an automated molecular docking platform based on AutoDock Vina and convolutional neuronal network (CNN)-based AI-assisted GNINA. Overall, the conventional molecular docking tool AutoDock Vina results showed that all tocotrienol isomers exhibited the strongest average binding affinities to VCAM-1. Among the isomers, α-tocotrienol displayed the highest binding affinity towards E-selectin (-6.69 ± 0.00 kcal/mol) and ICAM-1 (-6.79 ± 0.00 kcal/mol), whereas β-tocotrienol exhibited the strongest affinity toward VCAM-1 (-7.59 ± 0.00 kcal/mol) in the molecular docking analysis using conventional molecular docking tool AutoDock Vina. In contrast, the AI-assisted molecular docking tool GNINA leveraging deep learning, demonstrated a more accurate and consistent affinity profile by consistently identified β-tocotrienol as the most favorable binder toward E-selectin (-6.91 ± 0.01 kcal/mol) and ICAM-1 (-7.08 ± 0.90 kcal/mol), characterized by hydrogen bonding, hydrophobic interactions, and extensive van der Waals forces, that are crucial for the lipid-soluble ligand. The AI-assisted molecular docking tool GNINA docking for VCAM-1 was not generated due to structural limitations of the receptor model. Molecular dynamics (MD) simulations over 200 ns demonstrate a significant stabilizing interaction with GLU87, whereas the hydrogen bonding at ASP178 was found to be intermittent and contributory throughout the trajectory. This study provides the first comprehensive computational evidence differentiating the multi-target potency of tocotrienol isomers in targeting inflammatory and vascular-related pathways. Further experimental validation is warranted to confirm these in silico predictions and explore their biological significance. (Copyright © 2026 Elsevier Ltd. All rights reserved.) |
| Competing Interests: | Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Atherosclerosis; AutoDock Vina; Endothelial adhesion biomarker; GNINA; Molecular dynamics simulation; Tocotrienol |
| Substance Nomenclature: | 126547-89-5 (Intercellular Adhesion Molecule-1) 0 (Tocotrienols) 0 (E-Selectin) 0 (Vascular Cell Adhesion Molecule-1) |
| Entry Date(s): | Date Created: 20260529 Date Completed: 20260618 Latest Revision: 20260618 |
| Update Code: | 20260619 |
| DOI: | 10.1016/j.compbiolchem.2026.109136 |
| PMID: | 42214856 |
| Βάση Δεδομένων: | MEDLINE |
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