The identification of new ATAD2 bromodomain inhibitors: the application of combined ligand and structure-based virtual screening

Ligand-based virtual screening (LBVS) and structure-based virtual screening (SBVS) approaches were used to identify new inhibitors for ATAD2 bromodomain. The LBVS approach was used to search 23,129,083 clean compounds to identify compounds similar to an active compound with reported pIC50 equal to 7.2. Based on LBVS results, 19 compounds were selected. To perform SBVS, by applying nine filters on 23,129,083 clean compounds, 1,057,060 compounds were selected. After performing SBVS on these selected compounds with idock software, 16 compounds with the lowest binding energies were selected. More accurate molecular docking analysis was performed on these 35 selected compounds by using iGEMDOCK software and six of them with the lowest binding energies were selected as hit compounds. These compounds were zinc36647229, zinc77969074, zinc13637358, zinc77971540, zinc12991296 and zinc19374204.基于配体的虚拟筛选（Ligand-based virtual screening, LBVS）与基于结构的虚拟筛选（Structure-based virtual screening, SBVS）方法被用于识别ATAD2溴结构域（bromodomain）的新型抑制剂。研究采用LBVS方法检索23129083个纯净化合物，以筛选出与活性pIC₅₀为7.2的已知活性化合物结构相似的化合物。基于LBVS的筛选结果，共选取19个化合物。为开展SBVS，研究对23129083个纯净化合物施加九项筛选规则，得到1057060个候选化合物。使用idock软件对上述候选化合物完成SBVS后，选取结合能最低的16个化合物。随后，使用iGEMDOCK软件对上述35个选取的化合物开展更精准的分子对接分析，并从中选取结合能最低的6个作为命中化合物。上述命中化合物分别为zinc36647229、zinc77969074、zinc13637358、zinc77971540、zinc12991296及zinc19374204。