TY - Jour A2 - Mitchell，John Au - Xu，Dongfang Au - Xue，Guangpu Au - Peng，Bangya Au - Feng，Zanjie Au - Lu，Hungling Au - Gong，Lihu Py - 2020年 - 2020/05/22 Ti -高通量对接和分子动力学模拟鉴定人类凝血因子XIIA SP - 2852051 VL-2020 AB - 人凝血因子XIIA（FXIIA）是一种胰蛋白酶样丝氨酸蛋白酶，其参与病理血栓形成。作为设计安全抗凝剂的潜在目标，近年来，FXIIA已经获得了很多兴趣。在本研究中，我们在烯胺数据库中使用了500,064种化合物的虚拟高通量筛选，以获得FXIIA最潜在的抑制剂。随后，选择具有显着结合能量的18个化合物（从-65.195至-15.726kcal / mol），预测其撞击性能选择代表性抑制剂。三种化合物（Z1225120358，Z432246974和Z146790068）表现出优异的结合亲和力和可耐可性。进行FXIIA-LigAnd复合物的MD模拟，以揭示这三种化合物的稳定性和抑制机制。通过抑制活性因子XIIa测定，我们测试了五种化合物Z1225120358，Z432246974，Z45287215，Z30974175和Z146790068的活性，具有PIC50值 9.3 * 10. - 7. 那 3.0 * 10. - 5. 那 7.8 * 10. - 7. 那 8.7 * 10. - 7. ，和 1.3 * 10. - 6.  M, respectively; the AMDET properties of Z45287215 and Z30974175 show not well but have better inhibition activity. We also found that compounds Z1225120358, Z45287215, Z30974175, and Z146790068 could be more inhibition of FXIIa than Z432246974. Collectively, compounds Z1225120358, Z45287215, Z30974175, and Z146790068 were anticipated to be promising drug candidates for inhibition of FXIIa. SN - 1748-670X UR - https://doi.org/10.1155/2020/2852051 DO - 10.1155/2020/2852051 JF - Computational and Mathematical Methods in Medicine PB - Hindawi KW - ER -