In silico predication of nuclear hormone receptors for organic pollutants by homology modeling and molecular docking

Leukotrienes have been shown to be involved in a variety of diseases such as cardiovascular diseases, cancer, asthma, ulcerative colitis, and rhinitis. 5-Lipoxygenase-Activating Protein (FLAP) was found to be a key enzyme of leukotriene synthesis. Comparative Molecular Field Analysis (CoMFA) and molecular docking studies were carried out on a series of substituted 2,2-bisaryl-bicycloheptanes FLAP inhibitors. The docking results provided a reliable conformational alignment scheme for 3-D QSAR model. Based on the docking conformations, highly predictive CoMFA model was performed with a leave-one-out cross-validated q2 of 0.651. The noncross-validated analysis with four optimum components revealed a conventional r2 value of 0.972, F=175.674, and an estimated standard error of 0.169. The predictive ability of this model was validated by the testing set with a conventional r2 value of 0.920. The analyses may be used to design more potent FLAP inhibitors and predict their activities prior to synthesis.

Bing Wu, Yan Zhang, Jie Kong, Xuxiang Zhang, Shupei Cheng
December 1, 2009
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