College of General Education, Kookmin University, Seoul 02707, Republic of Korea.
J Mol Graph Model. 2024 Dec;133:108872. doi: 10.1016/j.jmgm.2024.108872. Epub 2024 Sep 27.
Human fatty acid-binding proteins (FABPs) are involved in many aspects of lipid metabolism, such as the uptake, transport, and storage of lipophilic molecules, as well as cellular functions. Understanding how FABPs recognize fatty acids (FAs) is crucial for identifying FABP function and applications, such as in inhibitor design or biomarker development. The recently developed AlphaFold3 (AF3) demonstrates significantly higher accuracy than other prediction tools, particularly in predicting protein-ligand interactions with state-of-the-art docking tools. Studies on whether AF3 can be used to identify the FAs of FABP are lacking. To assess the accuracy of FA docking to FABPs using AF3, models of FA docked into FABP generated using AF3 were compared with experimentally determined FA-bound FABP structures. FA ligands in AF3 structures docked reliably into the FA-binding pocket of FABPs; however, the detailed binding configuration of most FA ligands docked into FABPs and the interaction between FA and FABP determined using AF3 and experimentally differed. These results will aid in understanding FA docking to FABPs and other FA-binding proteins using AF3.
人脂肪酸结合蛋白（FABP）参与脂质代谢的许多方面，例如亲脂分子的摄取、运输和储存，以及细胞功能。了解 FABP 如何识别脂肪酸（FA）对于确定 FABP 的功能和应用至关重要，例如抑制剂设计或生物标志物开发。最近开发的 AlphaFold3（AF3）的准确性明显高于其他预测工具，特别是在使用最先进的对接工具预测蛋白质-配体相互作用方面。关于 AF3 是否可用于鉴定 FABP 的 FA 的研究尚缺乏。为了评估使用 AF3 对 FABP 进行 FA 对接的准确性，将使用 AF3 生成的 FA 对接 FABP 模型与实验确定的 FA 结合 FABP 结构进行比较。在 AF3 结构中，FA 配体可靠地对接入 FABP 的 FA 结合口袋中；然而，使用 AF3 和实验确定的大多数 FA 配体对接入 FABP 中的详细结合构型以及 FA 与 FABP 之间的相互作用存在差异。这些结果将有助于使用 AF3 理解 FA 对接入 FABP 和其他 FA 结合蛋白。
