Ice-binding surface of fish type III antifreeze

We employed computational techniques, including molecular docking, energy m inimization, and molecular dynamics simulation, to investigate the ice-bind ing surface of fish type III antifreeze protein (AFP). The putative ice-bin ding site was previously identified by mutagenesis, structural analysis, an d flatness evaluation. Using a high-resolution x-ray structure of fish type III AFP as a model, we calculated the ice-binding interaction energy of 11 surface patches chosen to cover the entire surface of the protein. These v arious surface patches exhibit small but significantly different ice-bindin g interaction energies. For both the prism ice plane and an "ice" plane in which water O atoms are randomly positioned, our calculations show that a s urface patch containing 14 residues (L19, V20, T18, S42, V41, Q9, P12, Ale, M21, T15, Q44, 113, N14, K61) has the most favorable interaction energy an d corresponds to the previously identified ice-binding site of type III AFP . Although in general agreement with the earlier studies, our results also suggest that the ice-binding site may be larger than the previously identif ied "core" cluster that includes mostly hydrophilic residues. The enlargeme nt mainly results from the inclusion of peripheral hydrophobic residues and K61.