title: Extensive simulations of the full-length matrix metalloproteinase-2 enzyme in a prereactive complex with a collagen triple-helical peptide.
abstract: 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.
authors.affiliation: Departamento de Química Física y Analítica, Universidad de Oviedo , Julián Clavería 8, Oviedo, Asturias, 33006 Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: Díaz
authors.forename: Dimas
authors.initials: D
authors.lastname: Suárez
mesh_terms: D003094:Collagen / Q000737:chemistry*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry*; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D046912:Multiprotein Complexes; D010455:Peptides; D003094:Collagen; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2