Xyloketal B, a marine compound, acts on a network of molecular proteins and regulates the activity and expression of rat cytochrome P450 3a: a bioinformatic and animal study

Su, Junhui; Chang, Cui; Xiang, Qi; Zhou, Zhi-Wei; Luo, Rong; Yang, Lun; He, Zhi-Xu; Yang, Hongtu; Li, Jianan; Bei, Yu; Xu, Jinmei; Zhang, Minjing; Zhang, Qihao; Su, Zhijian; Huang, Yadong; Pang, Jiyan; Zhou, Shu-Feng

The interactome of XKB was predicted using the DDI-CPI tool, a web-based server that can predict drug-drug interactions via the chemical-protein interactome. 23, 24 Protein targets were obtained from a third-party protein structure database named PDBbind. 25 There is a total of 1,780 Protein Data Bank (PDB) entries for human proteins available in PDBbind, and a total of 301 nonredundant PDBs corresponding to 353 ligand binding pockets were identified, 86% of which have resolutions of less than 2.5Ã…. The docking boxes for each of the pockets were defined by expanding the circumscribed cube of the pocket with a margin of 8Ã… in six directions (up, down, front, back, left, and right). For preparation of XKB, the two-dimensional structure of the XKB was downloaded from PubChem. The hydrogen and Gasteiger charge were added and the file format was transformed into mol2 using Vega ZZ. The docking program AutoDock 4.2 was used to dock the XKB molecule into all 353 pockets, generating a score vector of 353 dimensions. Z'-scores were then calculated using methodologies described elsewhere. 23, 26, 27 Herein, an empirical threshold of -0.6 for the Z'-score was set to indicate that the binding of XKB to this target was likely to be true.