title: Chain registry and load-dependent conformational dynamics of collagen.
abstract: Degradation of fibrillar collagen is critical for tissue maintenance. Yet, understanding collagen catabolism has been challenging partly due to a lack of atomistic picture for its load-dependent conformational dynamics, as both mechanical load and local unfolding of collagen affect its cleavage by matrix metalloproteinase (MMP). We use molecular dynamics simulation to find the most cleavage-prone arrangement of α chains in a collagen triple helix and find amino acids that modulate stability of the MMP cleavage domain depending on the chain registry within the molecule. The native-like state is mechanically inhomogeneous, where the cleavage site interfaces a stiff region and a locally unfolded and flexible region along the molecule. In contrast, a triple helix made of the stable glycine-proline-hydroxyproline motif is uniformly flexible and is dynamically stabilized by short-lived, low-occupancy hydrogen bonds. These results provide an atomistic basis for the mechanics, conformation, and stability of collagen that affect catabolism.
authors: Department of Biomedical Engineering and ‡Department of Materials Science and Engineering, Texas A&M University , College Station, Texas 77843, United States.
authors: Xiaojing
authors: X
authors: Teng
authors: Wonmuk
authors: W
authors: Hwang
mesh_terms: D003094:Collagen / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D020782:Matrix Metalloproteinases / Q000737:chemistry; D008962:Models, Theoretical; D056004:Molecular Dynamics Simulation; D011392:Proline / Q000737:chemistry; D011487:Protein Conformation
chemical_list: D003094:Collagen; D011392:Proline; D020782:Matrix Metalloproteinases