基于虚拟筛选与分子动力学模拟的方法探究潜在的半乳糖凝集素1的抑制剂

Exploring potent inhibitor of Galectin-1 via Virtual Screening and Molecular Dynamics Simulation

目的 :探究半乳糖凝集素-1(Gal-1)是否存在与小分子结合的位点,从中筛选出与Gal-1靶点特异性结合的分子。方法 :应用分子对接的方法,搜寻小分子抑制物与Gal-1结合的可能位点,并利用虚拟筛选从包含5963个化合物的数据库中针对潜在位点进行对接,然后对得分高的蛋白配体复合物进行分子动力学(MD)模拟及MMPBSA分析。结果 :位于Gal-1表面的口袋,ZINC000885764928与预测的口袋之间形成了较强的相互作用;虚拟筛选打分与MD模拟的参数证实了结合的稳定性。结论 :肝内胆管癌(ICC)标志蛋白Gal-1与ZINC000885764928,ZINC000095618662的结合具有保守性,ZINC000885764928和ZINC000095618662可以作为潜在Gal-1抑制剂的分子骨架。

Objective Explore whether galectin-1(Gal-1)has a site binding to small molecules,and select molecules that specifically bind to Gal-1 targets. Methods Molecular docking was applied to search for possible sites for small molecule inhibitors to bind to Gal-1,and virtual screening was used to dock potential sites from a database containing 5963 compounds,and then molecular dynamics(MD)simulations were performed on the protein ligand complex with high scores. Results Molecular docking was found to bind to the canyon-like pocket on the surface of Gal-1,and a strong interaction formed between zinc000885764928 and the predicted pocket;The parameters of the virtual screening score and MD simulation confirm the stability of the combination. Conclusion Intrahepatic cholangiocarcinoma(ICC)marker protein Gal-1 is conserved in binding to ZINC0008885764928 and ZINC000095618662. Besides,ZINC000885764928 and ZINC000095618662 can serve as molecular backbone for potential inhibitors of Gal-1.