Biomedical Engineering Reference
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Fig. 2.3
Conservation of the secondary structure of the MMP2 catalytic site during the 2 ns MD
simulation
conformational stability status for the simulated molecule. We have isolated the
obtained trajectories for the catalytic domain of MMP-2 in the 1QIB file and we
have analyzed the evolution of the secondary structure within simulation time.
The domains of the catalytic site showed a good conservation over simulation
time (Fig.
2.3
).
By performing a Root Mean Square Fluctuation (RMSF) analysis, we have com-
pared the NMR starting structure of the MMP2 catalytic site with the structures
obtained by molecular dynamics simulations and we have noticed a high stability
for this domain. The catalytic site stability was witnessed by the reduced fluctuations
for the catalytic Zn area. However we have noticed some fluctuations, mainly in
some loop regions near the catalytic site of the MMP, in 192-250 region of the
MMP2 PDB file (394-449 on drawing) (Fig.
2.4
).
Protein conformational changes are important mainly for enzymes and their
activation status. These conformational changes are part of the kinetic states for
proteins and include the variability of the secondary and tertiary structure and
thus the global atomic movement in the investigated protein-enzyme. At the
same time, side chain fluctuations and loop movements are characterizing the
kinetic states of the observed substates in molecular dynamics simulations.
MMP-2 shows a remarkable stability for the considered catalytic site and the
presence of two substates. The analysis of free Gibbs energy landscape for
MMP2 catalytic site showed a native state with two substates separated by less
than 1KT (Fig.
2.5
).
Thus, we have concluded that the dynamic signature for the MMP2 catalytic site
is a native state with two substates, in close vicinity. We have also studied the sec-
ondary structure conservation, root mean square deviation (RMSD), and fluctuation
cluster analysis for a full structured description of the crystal structure of the MMP-2
catalytic site. Based on these results, we can thus define new tricks for strategies
regarding MMP inhibitors design. The role of the atomic position in the catalytic
site for MMPs appear to be essential regarding to further simulations for conceiving
a rather modulating inhibitor for these enzymes.
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