MODELING OF COMPLEXES BETWEEN CYTOCHROME P450 1A2 AND SUBSTRATES
A. A. Pogrebnoy, M. A. Grishina, V. A. Potemkin
Keywords: docking, modeling, complex, substrate, x-ray diffraction analysis, P450, 1A2, 2HI4
Pages: 852-858
Abstract
Based on the 2HI4 complex taken from the PDB database, molecular docking of 17 substrates in the cytochrome P450 1A2 cavity is performed using the 3D-QSAR algorithm CiS. The arrangement of substrate molecules in the 1A2 isoform cavity is considered, the orientation of the molecular reaction centers relative to heme is analyzed, and the character of interaction between substrates and active site aminoacid residues is investigated. The structures of the modeled complexes allow us to explain metabolic pathways in demethylation reactions and some reactions of hydroxylation, which enables an application of the CiS algorithm to predict metabolic pathways.
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