临床口腔医学杂志2026，Vol.42Issue(1)：7-11,5.DOI:10.3969/j.issn.1003-1634.2026.01.003
基于分子对接和分子动力学模拟的FAP抑制剂筛选
Virtual screening of FAP inhibitors based on molecular docking and molecular dynamics simulation
摘要
Abstract
Objective:To identify novel fibroblast activation protein(FAP)inhibitors from the FDA-approved small-molecule library by molecular docking,thereby providing lead structures for the treatment of bone-destructive diseases such as periodontitis.Methods:AutoDock Vina was employed for initial virtual screening.The four top-ranking ligands(lowest bind-ing energies)were subjected to 100 ns molecular dynamics simulations with GROMACS,and the binding free energies were estimated by the molecular mechanics-Poisson-Boltzmann surface area(MM-PBSA)approach to assess stability and affinity.Results:A total of 818 compounds exhibited binding energies<-7 kcal/mol.Among the candidate molecules,Hit 1 and Hit 3 displayed the smallest root-mean-square deviation(RMSD)fluctuations,persistent hydrogen bonding,and the lowest MM-PBSA free energies(-121.6 and-165.6 kJ/mol).Conclusion:Hit 1 and Hit 3 represent high-affinity,high-stability FAP-inhibitory leads suitable for subsequent in-vitro activity validation and structural optimization.关键词
成纤维细胞活化蛋白/分子对接/分子动力学模拟/虚拟筛选/小分子抑制剂Key words
Fibroblast activation protein/Molecular docking/Molecular dynamics simulation/Virtual screening/Small-molecule inhibitors分类
医药卫生引用本文复制引用
彭君言,张星宇,陈美玲..基于分子对接和分子动力学模拟的FAP抑制剂筛选[J].临床口腔医学杂志,2026,42(1):7-11,5.基金项目
国家自然科学基金项目(编号:82571147) （编号:82571147）
湖北省自然科学基金项目(编号:2023AFB1038) （编号:2023AFB1038）
