Molecular Scissors: From Biomaterials Implant to Tissue Remodeling - Biologically Responsive Biomaterials for Tissue Engineering - page 23

Fig. 2.2 Root mean square displacement (RMSD) for backbone atoms on the 1QIB file, represent-
ing the catalytic site of MMP-2, during a 2 ns molecular dynamic simulation
It is demonstrated that various MMPs exhibit different selectivity for many
ECM proteins. Thus, it is important to understand such substrate selectivity to
develop new synthetic MMP inhibitors. We have also shown that not only the Zn
ion coordination in the P site is important, but also the hydrophobicity of S1
tunnel can be a step in further computer design for potent inhibitor or enzyme
modulation factors.
The stability of the catalytic domain was subject for many studies [ 4, 26, 27 ]
including our group investigation [ 92 ]. In order to appreciate this stability, we have
performed molecular dynamics (MD) simulations of the catalytic domain of a
known matrix metalloproteinase (MMP-2) for a 2 ns duration, in the absence of the
substrate or a known inhibitor, starting from Protein Data Bank published data
(ID-1QIB) [ 9 ]. We have chosen to the MMP2 (gelatinase A) catalytic domain, while
it is the best characterized crystallographically. We have evaluated the conforma-
tional stability for MMP2 catalytic site during MD simulation.
In order to describe the variation of atom position into the simulated structures
by comparison with the experimental defined conformation, it is necessary to plot
the Root Mean Square Displacement (RMSD) over time (Fig. 2.2 ). We have tried
to assess the stable states of the investigated by monitoring the RMSD of the pro-
tein backbone or only for the C-a carbon atoms along the trajectory, compared to
the structure before starting the simulation. Literature data [ 18, 26, 100 ] show that
RMSD values ranged between 0.1 nm and 0.3 nm, if constant, are representing a