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.

背景：维生素E由α，β，γ和δ-生育酚（Ts）和α，β，γ和δ-生育三烯酚（T3s）组成。维生素E具有神经保护抗氧化剂，抗癌和降低胆固醇的作用。除了αT被αT转移蛋白（αTTP）选择性转运外，这些异构体的细胞内运输仍然未知。

目的：本研究旨在通过计算机对接确定维生素E异构体与转运蛋白的结合。

方法：基于与αTTP相同的分子功能注释，使用AmiGo基因本体工具选择转运蛋白。蛋白质结构从蛋白质数据库获得。从ZINC数据库获得配体结构。使用SwissDock进行计算机对接。

结果与讨论：共发现6种转运蛋白：SEC14样蛋白2，糖脂转移蛋白（GLTP），含pleckstrin同源结构域的A族成员8，IV型胶原蛋白alpha-3结合蛋白，神经酰胺1磷酸盐转移蛋白和afamin。与其他转运蛋白相比，αTTP对除βT3以外的所有异构体的亲和力最高。维生素E异构体与αTTP的结合顺序为γT>βT>αT>δT>αT3>γT3>δT3>βT3。GLTP对生育三烯酚的亲和力高于生育酚。βT3与GLTP的结合强于αTTP。

结论：αTTP仍然是大多数异构体的最优选转运蛋白。αT对αTTP的结合亲和力并不比其他异构体最高，表明这些异构体的其他细胞内运输机制可能存在。GLTP可以介导生育三烯酚，特别是βT3的细胞内转运。这些异构体的生物利用度的提高可以增强它们对人类的有益作用。