Molecular dynamics simulations of the full triple helical region of collagen type I provide an atomic scale view of the protein's regional heterogeneity.
Collagen is a ubiquitous extracellular matrix protein. Its biological functions, including maintenance of the structural integrity of tissues, depend on its multiscale, hierarchical structure. Three elongated, twisted peptide chains of > 1000 amino acids each assemble into trimeric proteins characterized by the defining triple helical domain. The trimers associate into fibrils, which pack into fibers. We conducted a 10 ns molecular dynamics simulation of the full-length triple helical domain, which was made computationally feasible by segmenting the protein into overlapping fragments. The calculation included ~1.8 million atoms, including solvent, and took approximately 11 months using the CPUs of over a quarter of a million computers. Specialized analysis protocols and a relational database were developed to process the large amounts of data, which are publicly available. The simulated structures exhibit heterogeneity in the triple helical domain consistent with experimental results but at higher resolution. The structures serve as the foundation for studies of higher order forms of the protein and for modeling the effects of disease-associated mutations.
Department of Genetics, Stanford University, 1501 S. California Avenue, Palo Alto, CA 94304, USA.
Dale L
DL
Bodian
Randall J
RJ
Radmer
Sean
S
Holbert
Teri E
TE
Klein
D024042:Collagen Type I / Q000737:chemistry* / Q000235:genetics; D019295:Computational Biology; D003627:Data Interpretation, Statistical; D030562:Databases, Protein; D006801:Humans; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012984:Software
D024042:Collagen Type I; D010446:Peptide Fragments