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Extensive Simulations of the Full-Length Matrix Metalloproteinase-2 Enzyme in a Prereactive Complex with a Collagen Triple-Helical Peptide
- Díaz, Natalia, Suárez, Dimas
- Biochemistry 2015 v.54 no.5 pp. 1243-1258
- active sites, collagen, entropy, gelatinase A, hydrolysis, mechanics, models, molecular dynamics
- Collagen hydrolysis catalyzed by matrix metalloproteinases is an important and complex process involved in a variety of physiological and pathological conditions. To contribute to its characterization at the molecular level, herein we analyze three different models for the complex formed between the full-length matrix metalloproteinase-2 (MMP-2) enzyme and a synthetic triple-helical peptide (fTHP-5). The considered MMP-2/fTHP-5 complexes mainly differ in the location of the C-terminal hemopexin-like domain, but in all of them, the middle α-chain of the substrate (B-chain) is placed within the active site groove. We performed extended molecular dynamics (MD) simulations to determine the most likely rearrangements of the MMP-2 domains in response to the presence of the triple helix. The relative stability of the MD models is assessed in terms of molecular mechanics Poisson–Boltzmann calculations and approximate estimations of configurational entropy. In addition, the most significant MMP-2···fTHP-5 interactions at the catalytic and noncatalytic domains are also analyzed to gather some clues about the role of the different domains during collagenolysis.