Matrix Metalloproteinase (MMP) -13 or Collagenase - 3 plays a significant role in the formation and remodeling of bone, tumor invasion and causes osteoarthritis. Water molecular dynamic studies of the five (1XUC, 1XUD, 1XUR, 456C, 830C) PDB and solvated structures of MMP-13 in human have been carried out upto 5 ns on assigning the differential charges (+2, +1, +0.5 e) to both the Zinc ions. The MM and MD-studies have revealed the coordination of three water molecules (W_H, W_I and W_S) to Zn_c and one water to Zn_s . The transition of geometry around the Zn_c from tetrahedral to octahedral via trigonal bipyramidal, and for Zn_s from tetrahedral to trigonal bipyramidal are seem interesting. Recognition of two zinc ions through water molecular bridging (Zn_c – W_H (W₁)...W₂ ….W₃ ….H₁₈₇ - Zn_s) and the stabilization of variable coordination geometries around metal ions may indicate the possible involvement of Zn_c …Zn_s coupled mechanism in the catalytic process. So the hydrophilic topology and stereochemistry of water mediated coupling between Zn-ions may provide some plausible hope towards the design of some bidentate/polydentate bridging ligands or inhibitors for MMP-13.

This article can be cited as:
B. Chakrabarti, H. R Bairagya, P. Mallik, B. P Mukhopadhyay, A. K Bera, An Insight to Conserved Water Molecular Dynamics of Catalytic and Structural Zn⁺² ions in Matrix Metalloproteinase 13 of Human, J Biomol Struct Dyn 28(4), 503-516 (2011).