In Silico Docking of Vitamin E Isomers on Transport Proteins

Author(s): Nurul Syeefa Zulkiflee, Siti Amilia Awang, Woo Xian Ming, Muhammad Fauzan Wira’i Kamilan, M Yuveneshwari Mariappan, Tan Jen Kit*

Journal Name: Current Computer-Aided Drug Design

Volume 16 , Issue 4 , 2020


DOI : 10.2174/1573409915666190614113733

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Abstract:

Background: Vitamin E is comprised of α, β, γ and δ-tocopherols (Ts) and α, β, γ and δ- tocotrienols (T3s). Vitamin E has neuroprotective antioxidant, anti-cancer, and cholesterol-lowering effects. Intracellular trafficking of these isomers remains largely unknown, except for αT which is selectively transported by αT transfer protein (αTTP).

Objective: This study aimed to determine the binding of vitamin E isomers on transport proteins using in silico docking.

Methods: Transport proteins were selected using AmiGo Gene Ontology tool based on the same molecular function annotation as αTTP. Protein structures were obtained from the Protein Data Bank. Ligands structures were obtained from ZINC database. In silico docking was performed using SwissDock.

Results and Discussion: A total of 6 transport proteins were found: SEC14-like protein 2, glycolipid transfer protein (GLTP), pleckstrin homology domain-containing family A member 8, collagen type IV alpha-3-binding protein, ceramide-1-phosphate transfer protein and afamin. Compared with other transport proteins, αTTP had the highest affinities for all isomers except βT3. Binding order of vitamin E isomers toward αTTP was γT > βT > αT > δT > αT3 > γT3 > δT3 > βT3. GLTP had a higher affinity for tocotrienols than tocopherols. βT3 bound stronger to GLTP than αTTP.

Conclusion: αTTP remained as the most preferred transport protein for most of the isomers. The binding affinity of αT toward αTTP was not the highest than other isomers suggested that other intracellular trafficking mechanisms of these isomers may exist. GLTP may mediate the intracellular transport of tocotrienols, especially βT3. Improving the bioavailability of these isomers may enhance their beneficial effects to human.

Keywords: Tocopherols, tocotrienols, carrier proteins, molecular docking simulation, αTTP, GLTP.

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Article Details

VOLUME: 16
ISSUE: 4
Year: 2020
Published on: 02 September, 2020
Page: [467 - 472]
Pages: 6
DOI: 10.2174/1573409915666190614113733
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