Molecular Scissors: From Biomaterials Implant to Tissue Remodeling - Biologically Responsive Biomaterials for Tissue Engineering - page 27

Fig. 2.6 Final re fi ned
complex fi nal MMP2
(hemopexinic)—TIMP2, with
the choice of the position
with the most favorable score
for docking
(RMSd), the distance between the initial atom coordinates in the crystallographic
structure and the final coordinates of the partially altered structures by the modeling
process. RMSd values of 2.30 Å indicated a correct superimposition and validated
the method for further enzyme inhibitor pairs. After model refinement, we have
represented the results with VMD viewer [ 53 ]. We have represented the final com-
plexes MMP-2 (catalytic-refined)-TIMP-2 (Fig. 2.6 ) and MMP2 (hemopexinic-
re fi ned)-TIMP2 (Fig. 2.7 ).
MMP-9-TIMP-2 model raised some problems while PDB databases do not
include yet a crystallographic model but only a theoretical one. The chosen
model was 1LKG. In PDB database we have selected the hemopexinic domains
(1ITV-dimeric form) and catalytic (1L6J) [ 9 ]. The 1L6J file contains the whole
MMP9 sequence from which we have selected the catalytic domain for the
experimental model. The domains were superimposed over the theoretical model
for MMP-9 (Fig. 2.8 ).
The docking procedure for the MMP9-TIMP2 complex determined 10,000 pos-
sible variants that have been filtered and selected from the minimal coupling energy
then graphically represented. Following this molecular docking study we have
concluded that the natural inhibitor TIMP2 has a higher affinity for the catalytic