Paper Citing NAMD - Abstract
Chakrabarti, Bornali; Bairagya, Hridoy R.; Mallik, Payel; Mukhopadhyay, Bishnu P.; Bera, Asim K.
An Insight to Conserved Water Molecular Dynamics of Catalytic and Structural Zn+2 ions in Matrix Metalloproteinase 13 of Human
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, 28:503-516, FEB 2011
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-1 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(W-1)center dot center dot center dot W-2 center dot center dot center dot center dot W-3 center dot center dot center dot center dot H-187-Zn-s) and the stabilization of variable coordination geometries around metal ions may indicate the possible involvement of Zn-c center dot center dot center dot 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.
