Docking study of matrix metalloproteinase inhibitors


J. Ryška1, S. K. Mishra1, R. Svobodová Vařeková1 and J. Koča1


1 National Centre for Biomolecular Research, Faculty of Science, Masaryk University,

Kamenice 5, 625 00 Brno-Bohunice, Czech Republic


Matrix metalloproteinases (MMPs) are a family of zinc-containing, calcium-dependent enzymes responsible for the remodelling and degradation of almost all components of the extracellular matrix [1]. They are known to be involved in a number of physiological and pathological cellular processes, such as wound healing, tumor growth and metastasis. MMP inhibitors have been explored as potential anticancer, anti-inflammatory and antiviral agents [2, 3].

With ongoing increase of computing power, in silico methods have become a key component of the rational drug design process. Molecular docking is one of the common computational techniques to predict preferred orientation of a small molecule in complex with a protein and to quantify its binding energy. Given the fact that MMPs are promising pharmaceutical targets, it is important to have a reliable docking method, which is able to rank the binding strength of ligands when also interactions established with ions presented in the system are taken into consideration. This is because one of the challenges in ligand-MMP docking is the presence of a zinc ion in the binding site. It has been shown that determining the correct orientation of the zinc-binding group is crucial to obtain preferred binding mode [4].

In this study we compare the docking accuracy of several contemporary molecular docking programs on several members of MMP family. The test set consists of 38 MMP-ligand complexes taken from the RCSB Protein Data Bank. Docking of the geometry optimized ligands was performed using several commonly used docking software. The docking results were correlated with experimental data. Performance of docking programs will be discussed in terms of their binding orientation and binding affinity prediction accuracy.


1.     C. E. Brinckerhoff, L. M. Matrisian, Nat. Rev. Mol. Cell Biol., 3 (2002) 207­­–214.

2.     C. T. Supuran, A. Casini, A. Scozzafava, Med. Res. Rev., 23 (2003) 535–558.

3.     G. Dorman,  C. Cseh, I. Hajdu, L. Barna, D. Konya, K. Kupai, L. Kovacs, P. Ferdinandy, Drugs, 70 (2010) 949–964.

4.     X. Hu, W. H. Shelver, Journal of Molecular Graphics and Modelling, 22 (2003) 115–126.