Solution- and adsorbed-state structural ensembles predicted for the statherin-hydroxyapatite system.

Area of Science:

• Biophysics
• Computational Biology
• Materials Science

Background:

• Understanding protein behavior at mineral interfaces is crucial for biomineralization.
• Statherin is a key protein in regulating calcium phosphate formation.
• Accurate structure prediction of proteins in different states is challenging.

Purpose of the Study:

• To develop and validate a multiscale structure prediction technique for biomineralization proteins.
• To investigate the solution and adsorbed-state ensembles of statherin.
• To compare computational predictions with experimental data.

Main Methods:

• Developed a Metropolis Monte Carlo-plus-minimization algorithm for protein structure prediction.
• Applied the technique to statherin in solution and adsorbed onto hydroxyapatite (HAp) crystal surfaces.
• Performed unbiased (blind) and biased simulations incorporating solid-state NMR data.

Main Results:

• The prediction technique accurately captured experimentally observed structural features of statherin.
• Minimal structural changes were observed upon statherin adsorption to HAp, with a notable folding event in the helical binding domain.
• Structurally promiscuous binding of statherin to different HAp crystal faces was predicted.
• Biased simulations suggested an alternative interpretation of some ssNMR data, potentially indicating intermolecular interactions.

Conclusions:

• The multiscale structure prediction method is effective for studying protein ensembles at biomineral interfaces.
• Statherin exhibits specific folding and binding behaviors at HAp interfaces.
• Combining ssNMR and structure prediction can yield high-resolution protein structures at biomineral interfaces.