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VOL. 73 (3), 703-746, 2007 ARE ADRENOMEDULLIN POSITIVE MODULATORS NOVEL...

TABLE 3. Different entries of the MMP-2 deposited in the Protein Data Bank

Pdb Information Experimental Method Reference
Code and Resolution

1ck7 Full length protein X-Ray (2.80 Å) (35)
1eak X-Ray (2.66 Å) (36)
1qib Catalytic domain X-Ray (2.80 Å) (37)
(inactive and mutant)
1gxd X-Ray (3.10 Å) (38)
1hov Catalytic domain with the NMR (11 models) (32)
inhibitor Batimastat
(not resolved)

ProMMP-2/TIMP-2 complex
(inactive)

Catalytic domain with
inhibitor SC-74020 (i52)

complex

All models were selected for docking procedures. For docking
purposes, the protonation state of histidines and glutamates in the
binding site was maintained as it was in the NMR structure. Both
zinc and calcium heteroatoms were kept throughout the docking
study.

Ligand Processing

All the ligands (series 1, 2 and 3, together with compound i52;
Figure 2 and Table 2) were used in its neutral protonation state.
Assignment of the atom types and charge calculations were
performed by using Sybyl 7.2. A conformational analysis was first
performed to all compounds to be docked by use of the program
Macromodel (24) and the Monte Carlo methodology. The parameters
given to Macromodel were set to default with some exceptions. The
force field selected was OPLS-AA. GS/SA solvation model was
selected. The program was set to explore trough 1000 steps modifying
three torsional angles each step. The limit of acceptance was set
to 50 kJ/mol above the instant minimum found. The minimization
method selected was conjugated gradient. The convergence RMS was
set to a limit of 2 Å. The criteria of minimization convergence was
set to 0.05 kJ/ Å-mol.

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