title: Solution- and adsorbed-state structural ensembles predicted for the statherin-hydroxyapatite system.
abstract: We have developed a multiscale structure prediction technique to study solution- and adsorbed-state ensembles of biomineralization proteins. The algorithm employs a Metropolis Monte Carlo-plus-minimization strategy that varies all torsional and rigid-body protein degrees of freedom. We applied the technique to fold statherin, starting from a fully extended peptide chain in solution, in the presence of hydroxyapatite (HAp) (001), (010), and (100) monoclinic crystals. Blind (unbiased) predictions capture experimentally observed macroscopic and high-resolution structural features and show minimal statherin structural change upon adsorption. The dominant structural difference between solution and adsorbed states is an experimentally observed folding event in statherin's helical binding domain. Whereas predicted statherin conformers vary slightly at three different HAp crystal faces, geometric and chemical similarities of the surfaces allow structurally promiscuous binding. Finally, we compare blind predictions with those obtained from simulation biased to satisfy all previously published solid-state NMR (ssNMR) distance and angle measurements (acquired from HAp-adsorbed statherin). Atomic clashes in these structures suggest a plausible, alternative interpretation of some ssNMR measurements as intermolecular rather than intramolecular. This work demonstrates that a combination of ssNMR and structure prediction could effectively determine high-resolution protein structures at biomineral interfaces.
authors.affiliation: Program in Molecular Biophysics, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Masica
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Gray
mesh_terms: D000327:Adsorption; D000465:Algorithms; D001665:Binding Sites; D003198:Computer Simulation; D017886:Durapatite / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D009010:Monte Carlo Method; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012471:Salivary Proteins and Peptides / Q000737:chemistry* / Q000378:metabolism; D055672:Static Electricity; D013329:Structure-Activity Relationship
chemical_list: C018149:STATH protein, human; D012471:Salivary Proteins and Peptides; D017886:Durapatite