Ice-binding surface of fish type III antifreeze

Area of Science:

• Biophysics
• Structural Biology
• Computational Chemistry

Background:

• Fish antifreeze proteins (AFPs) prevent cold shock by inhibiting ice crystal growth.
• Type III AFP is a small, globular protein with a known, but not fully characterized, ice-binding site.

Purpose of the Study:

• To computationally investigate and refine the understanding of the ice-binding surface of fish type III antifreeze protein (AFP).
• To identify specific residues and surface patches responsible for ice binding.

Main Methods:

• Utilized molecular docking, energy minimization, and molecular dynamics simulations.
• Calculated ice-binding interaction energies for 11 surface patches of type III AFP using its x-ray structure.
• Evaluated interactions with both prism and randomly positioned water planes.

Main Results:

• A 14-residue surface patch (including L19, V20, T18, S42, V41, Q9, P12, A16, M21, T15, Q44, I13, N14, K61) exhibited the most favorable ice-binding interaction energy.
• This optimal patch aligns with the previously identified ice-binding site.
• The calculated ice-binding site appears larger than previously defined core clusters, incorporating peripheral hydrophobic residues and K61.

Conclusions:

• Computational methods confirm and refine the location of the ice-binding site on fish type III AFP.
• The ice-binding site may be more extensive than previously thought, involving both hydrophilic and hydrophobic residues.
• This detailed understanding of AFP-ice interactions can inform the design of novel cryoprotectants.