Molecular dynamics simulation of matrix metalloproteinase 2: fluctuations and time evolution of recognition pockets.

We report a molecular dynamics simulation study of a zinc-protease--gelatinase A or MMP2--which is a major target for drug design, being involved in tumor metastasis and other degenerative diseases. Two structures have been employed as starting conditions, one based on the crystal of multi-domain proMMP2, the other consisting of the catalytic domain only. The overall fold of the two models is maintained over the 1260 ps trajectory, enabling us to analyze correlations of fluctuations among domains, and to observe the presence of correlations within the catalytic domain in the multi-domain enzyme only, hence due to the presence of hemopexin and fibronectin domains.