基于分子对接和分子动力学模拟的FAP抑制剂筛选OA
Virtual screening of FAP inhibitors based on molecular docking and molecular dynamics simulation
目的:基于分子对接方法从美国食品药品监督管理局(FDA)认证小分子库中快速发现新型成纤维细胞活化蛋白(fibroblast activation protein,FAP)抑制剂,为牙周炎等骨破坏疾病提供先导结构.方法:采用AutoDock Vina分子对接初筛,对结合能前 4 名候选小分子进行 100 ns GROMACS分子动力学模拟,并以分子力学-泊松-玻尔兹曼表面积(molecular mechanics Poisson-Boltzmann surface area,MM-PBSA)计算结合自由能,评价稳定性与亲和力.结果:818 个化合物结合能<-7 kcal/mol;候选小分子Hit 1 与Hit 3 在模拟中均方根偏差(root-mean-square deviation,RMSD)波动最小,氢键持续存在,MM-PBSA自由能最低(-121.6 与-165.6 kJ/mol).结论:Hit 1、Hit 3 为具高亲和力、高稳定性的FAP抑制剂先导,可进入体外活性验证及结构优化.
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.
彭君言;张星宇;陈美玲
华中科技大学同济医学院附属同济医院口腔医学中心华中科技大学同济医学院口腔医学院 湖北 武汉 430030华中科技大学同济医学院附属同济医院口腔医学中心华中科技大学同济医学院口腔医学院 湖北 武汉 430030华中科技大学同济医学院附属同济医院口腔医学中心华中科技大学同济医学院口腔医学院 湖北 武汉 430030
医药卫生
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
Fibroblast activation proteinMolecular dockingMolecular dynamics simulationVirtual screeningSmall-molecule inhibitors
《临床口腔医学杂志》 2026 (1)
7-11,5
国家自然科学基金项目(编号:82571147)湖北省自然科学基金项目(编号:2023AFB1038)
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