By means of molecular modeling and docking studies, two novel non-peptide inhibitors (pyrogallic acid and myricetin) with a new zinc binding group (ZBG) have been evaluated as inhibitors of NIMP-1 and NIMP-3. The differences in binding affinities for MMP-1 and MMP-3 have been rationalized, and the results are consistent with the experiments of Fang et al. The density functional theory (DFT) method B3LYP/6-31G* has also been employed to characterize the interactions between ZBG of pyrogallic acid and the catalytic zinc ion in MMP-1. Our results may be useful for further research in the structure-based design of inhibitors with improved potency and selectivity. (C) 2008 Elsevier Ltd. All rights reserved.