Successfully Docking to Proteins with Metal Ions
Many enzyme targets have metal ions in their active sites that play key roles in substrate binding and catalysis. A recent paper in Proteins investigated how AutoDock performed in docking to a variety of adenylyl cyclase toxins, with Mg2+ and Zn2+ ions in their active sites. Getting the right protonation state on the ligands and the right charges on the metal are key to success.
Chen et al. compared how AutoDock 3.05., LigandFit/Cerius2 4.10 and FlexX (in SYBYL 7.0) performed in docking of substrate analogues and inhibitors into the active sites of the crystal structures of EF (Edema Factor) , CyaA and mammalian adenylate cyclase. They concluded that when charges on the bound metal were set correctly, AutoDock was the most reliable in positioning the substrate analogues, and ranking the compounds, compared to experimental inhibition data against EF.
Chen, D., Menche, G., Power, T.D., Sower, L., Peterson, J.W. and Schein, C.H. (2007) "Accounting for ligand-bound metal ions in docking small molecules on adenylyl cyclase toxins." Proteins, 2007. 67(3): 593-605.