Alsulami Ali F
Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
Comput Biol Med. 2025 Feb;185:109588. doi: 10.1016/j.compbiomed.2024.109588. Epub 2024 Dec 19.
Understanding the multifaceted role of hallmark gene mutations in cancer progression is critical for developing targeted therapies. This study comprehensively analyses 344 hallmark gene mutations by mapping them to their three-dimensional protein structures using PDB data and AlphaFold models. Mutations were classified based on their locations, such as protein interfaces, ligand-binding sites, dimer interfaces, protein-DNA interfaces, and core regions. The results reveal that highly frequent mutations are located on the ligand-binding site and protein interface, highlighting their significant impact on protein function and interactions. This holistic approach bridges gaps in existing research, offering insights into the structural impacts of genetic alterations in hallmark genes, thereby informing more effective therapeutic strategies.
了解标志性基因突变在癌症进展中的多方面作用对于开发靶向治疗至关重要。本研究通过使用蛋白质数据银行（PDB）数据和阿尔法折叠（AlphaFold）模型将344个标志性基因突变映射到其三维蛋白质结构上，对这些突变进行了全面分析。根据突变位置进行分类，如蛋白质界面、配体结合位点、二聚体界面、蛋白质-DNA界面和核心区域。结果表明，高频突变位于配体结合位点和蛋白质界面，突出了它们对蛋白质功能和相互作用的重大影响。这种整体方法弥合了现有研究中的差距，为标志性基因遗传改变的结构影响提供了见解，从而为更有效的治疗策略提供依据。
