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MARIO A. GARCÍA Y COLS. AN. R. ACAD. NAC. FARM.

Tetrahedrical Square-based Trigonal bipyramidal Octahedrical
coordination pyramidal coordination coordination coordination

FIGURE 3. Different geometries for the coordination of the Zn2+ ion found in
the bibliography for proteases zinc-dependent. MMPIs are found to coordinate
by square-based pyramidal or trigonal bipyramidal geometry (19, 28). Zinc is the
center ion and the donnor atoms are in coordinating position. Coordinating atoms

in MMP are 3 His and one or two atoms of the ligand.

RESULTS

MMP-2 Selection

Five structures corresponding to MMP-2 subtype metalloproteinase
are found in the Brookhaven Protein Data Bank (31), as shown in
Table 3. No X-ray structures of MMP-2-Inhibitor complexes have been
reported so far, and the PDB codes 1ck7 and 1qib corresponding to
active MMP-2 exhibit low resolution values (2.80 Å). Only the NMR
structure with PDB code 1hov corresponds to a complex with a
hydroxamic acid inhibitor (i52, see Figure 2). For this reason it was
considered as the host structure for docking purposes. The eleven
models that contain the PDB 1hov (M1, M2,… M11) were considered
in the subsequent docking studies, as it would allow to reflect the
dynamic nature of MMP-2 in an aqueous environment.

Conformational Search and Docking

The series of compounds is characterized by the hydrocarbonated
chain that joins the two potential ZBG, which means, that all
compounds have at least 10 rotatable bonds. A torsional problem has
been reported finding good docked hits when the rotatable

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