, Volume 16, Issue 12, pp 1919-1929
Date: 17 Mar 2010

Modeling the binding modes of stilbene analogs to cyclooxygenase-2: a molecular docking study

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Abstract

Stilbene analogs are a new class of anti-inflammatory compounds that effectively inhibit COX-2, which is the major target in the treatment of inflammation and pain. In this study, docking simulations were conducted using AutoDock 4 software that focused on the binding of this class of compounds to COX-2 protein. Our aim was to better understand the structural and chemical features responsible for the recognition mechanism of these compounds, and to explore their binding modes of interaction at the active site by comparing them with COX-2 co-crystallized with SC-558. The docking results allowed us to provide a plausible explanation for the different binding affinities observed experimentally. These results show that important conserved residues, in particular Arg513, Phe518, Trp387, Leu352, Leu531 and Arg120, could be essential for the binding of the ligands to COX-2 protein. The quality of the docking model was estimated based on the binding energies of the studied compounds. A good correlation was obtained between experimental logAr values and the predicted binding energies of the studied compounds.

Figure

The interaction of thirty stilbene analogs to COX-2 protein was studied using the automated docking simulation. The results of this study showed that the analogs can adopt two different binding modes in the active site of the COX-2 protein and that their predicted binding energies are in agreement with their experimental logAr values.