Fatty acid transport protein 1 (FATP1) is an integral transmembrane protein that is involved in facilitating the translocation of long-chain fatty acids (LCFA) across the plasma membrane, thereby orchestrating the importation of LCFA into the cell. FATP1 also functions as an acyl-CoA ligase, catalyzing the ATP-dependent formation of fatty acyl-CoA using LCFA and VLCFA (very-long-chain fatty acids) as substrates. It is expressed in various types of tissues and is involved in the regulation of crucial signalling pathways, thus playing a vital role in numerous physiological and pathological conditions. Structural insight about FATP1 is, thus, extremely important for understanding the mechanism of action of this protein and developing efficient treatments against its anomalous expression and dysregulation, which are often associated with pathological conditions such as breast cancer. As of now, there has been no prior prediction or evaluation of the 3D configuration of the human FATP1 protein, hindering a comprehensive understanding of the distinct functional roles of its individual domains. In our pursuit to unravel the structure of the most commonly expressed isoforms of FATP1, we employed the cutting-edge ALPHAFOLD 2 model for an initial prediction of the entire protein’s structure. This prediction was complemented by molecular dynamics simulations, focusing on the most promising model. We predicted the structure of FATP1 in silico and thoroughly refined and validated it using coarse and molecular dynamics in the absence of the complete crystal structure. Their relative dynamics revealed the different properties of the characteristic FATP1.

中文翻译：

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使用 AlphaFold 对脂肪酸转运蛋白 1 进行基于人工智能的同源建模：结构阐明和分子动力学探索


脂肪酸转运蛋白 1 (FATP1) 是一种完整的跨膜蛋白，参与促进长链脂肪酸 (LCFA) 穿过质膜的易位，从而协调 LCFA 进入细胞。 FATP1 还充当酰基辅酶 A 连接酶，使用 LCFA 和 VLCFA（极长链脂肪酸）作为底物催化 ATP 依赖性脂肪酰基辅酶 A 的形成。它在各种类型的组织中表达，参与关键信号通路的调节，从而在许多生理和病理条件下发挥重要作用。因此，了解 FATP1 的结构对于理解该蛋白质的作用机制以及开发针对其异常表达和失调的有效治疗方法极其重要，这些异常表达和失调通常与乳腺癌等病理状况相关。截至目前，尚未对人类 FATP1 蛋白的 3D 构型进行预测或评估，这阻碍了对其各个结构域的独特功能作用的全面理解。在我们寻求解开 FATP1 最常见表达亚型的结构的过程中，我们采用了尖端的 ALPHAFOLD 2 模型来初步预测整个蛋白质的结构。这一预测得到了分子动力学模拟的补充，重点关注最有前途的模型。我们通过计算机预测了 FATP1 的结构，并在缺乏完整晶体结构的情况下使用粗略动力学和分子动力学对其进行了彻底的精炼和验证。它们的相对动态揭示了特征性 FATP1 的不同特性。