CINTESIS@RISE/Faculty of Sciences and Technology, University of the Algarve, Faro, Portugal.
Methods Mol Biol. 2025;2871:115-128. doi: 10.1007/978-1-0716-4217-7_11.
FOXO3 is integral in regulating numerous genes involved in critical cellular processes such as apoptosis, oxidative damage protection, cell growth, and cancer. Consequently, modulating FOXO3 activity holds significant potential for applications in cancer treatment and cellular aging. A promising approach involves identifying small-molecule modulators that can either enhance or inhibit FOXO3's DNA-binding capability. This paper details a virtual screening protocol aimed at discovering such modulators. Utilizing the crystal structures of FOXO3 in both its free and DNA-bound forms, we pinpoint potential binding sites that may disrupt or facilitate the DNA-FOXO3 interaction. A comprehensive virtual screening of a small-molecule compound library is conducted using AutoDock Vina software. The highest-ranking hits for each site are carefully selected and analyzed to determine their binding modes. This protocol paves the way for identifying novel modulators of FOXO3, offering therapeutic avenues in cancer and aging-related research.
FOXO3 是调节许多参与关键细胞过程的基因的重要组成部分，如细胞凋亡、氧化损伤保护、细胞生长和癌症。因此，调节 FOXO3 的活性在癌症治疗和细胞衰老方面具有重要的应用潜力。一种很有前途的方法是鉴定小分子调节剂，这些调节剂可以增强或抑制 FOXO3 的 DNA 结合能力。本文详细介绍了一种发现此类调节剂的虚拟筛选方案。利用 FOXO3 在自由和 DNA 结合两种形式的晶体结构，我们确定了可能破坏或促进 DNA-FOXO3 相互作用的潜在结合位点。使用 AutoDock Vina 软件对小分子化合物文库进行全面的虚拟筛选。仔细选择并分析每个位点的排名最高的命中物，以确定它们的结合模式。该方案为鉴定 FOXO3 的新型调节剂铺平了道路，为癌症和与衰老相关的研究提供了治疗途径。
