药效团
数量结构-活动关系
化学
基质金属蛋白酶抑制剂
立体化学
对接(动物)
蛋白质数据库
基质金属蛋白酶
计算生物学
生物化学
生物
医学
护理部
作者
Kely Medeiros Turra,Diogo Pineda Rivelli,Sílvia Berlanga de Moraes Barros,Kerly Fernanda Mesquita Pasqualoto
标识
DOI:10.1002/minf.201600004
摘要
A receptor-independent (RI) four-dimensional structure-activity relationship (4D-QSAR) formalism was applied to a set of sixty-four β-N-biaryl ether sulfonamide hydroxamate derivatives, previously reported as potent inhibitors against matrix metalloproteinase subtype 9 (MMP-9). MMP-9 belongs to a group of enzymes related to the cleavage of several extracellular matrix components and has been associated to cancer invasiveness/metastasis. The best RI 4D-QSAR model was statistically significant (N=47; r2=0.91; q2=0.83; LSE=0.09; LOF=0.35; outliers=0). Leave-N-out (LNO) and y-randomization approaches indicated the QSAR model was robust and presented no chance correlation, respectively. Furthermore, it also had good external predictability (82 %) regarding the test set (N=17). In addition, the grid cell occupancy descriptors (GCOD) of the predicted bioactive conformation for the most potent inhibitor were successfully interpreted when docked into the MMP-9 active site. The 3D-pharmacophore findings were used to predict novel ligands and exploit the MMP-9 calculated binding affinity through molecular docking procedure.
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