Akt1（蛋白激酶 B）因其在多种细胞过程中的重要功能而成为人们关注的焦点，并且抑制 Akt1 可以有效减少癌细胞中的肿瘤生长。在目前的工作中，我们通过使用多种计算技术，即基于药效团的虚拟筛选、分子对接、结合自由能计算和 ADME 特性，发现了一组新型 Akt1 抑制剂。使用 AADRR38 实施并验证了五点药效团假设。获得的 R2 和 Q2 值分别处于可接受的范围内，值分别为 0.90 和 0.64。生成的药效团模型用于虚拟筛选，以找出潜在的 Akt1 抑制剂。此外，对选定的命中进行分子对接、结合自由能分析，并使用 ADME 特性进行精炼。此外，我们通过包含从数据库获得的命中的结构特征，设计了一系列 6-甲氧基苯并[b]恶唑类似物。发现分子 D1-D10 具有较强的结合相互作用和较高的结合自由能值。此外，还进行了分子动力学模拟，以了解蛋白质-配体复合物的构象变化。© 2024。作者，获得 Springer Nature Switzerland AG 的独家许可。

Akt1 (protein kinase B) has become a major focus of attention due to its significant functionality in a variety of cellular processes and the inhibition of Akt1 could lead to a decrease in tumour growth effectively in cancer cells. In the present work, we discovered a set of novel Akt1 inhibitors by using multiple computational techniques, i.e. pharmacophore-based virtual screening, molecular docking, binding free energy calculations, and ADME properties. A five-point pharmacophore hypothesis was implemented and validated with AADRR38. The obtained R2 and Q2 values are in the acceptable region with the values of 0.90 and 0.64, respectively. The generated pharmacophore model was employed for virtual screening to find out the potential Akt1 inhibitors. Further, the selected hits were subjected to molecular docking, binding free energy analysis, and refined using ADME properties. Also, we designed a series of 6-methoxybenzo[b]oxazole analogues by comprising the structural characteristics of the hits acquired from the database. Molecules D1-D10 were found to have strong binding interactions and higher binding free energy values. In addition, Molecular dynamic simulation was performed to understand the conformational changes of protein-ligand complex.© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.