Computational modeling of antifreeze protein-ice interactions

Antifreeze proteins (AFPs) are a group of structurally very diverse proteins with the unique capability of binding to specific planes of seed ice crystals and inhibiting ice crystal growth. Although significant progress has been made in the identification of different families of these proteins, the molecular mechanism of their action is unclear. Initially, hydrogen bonding between the threonine residues of AFP Type I from winter flounder (HPLC6) and the water molecules in the ice surface had been suggested as the mechanism for its interaction with ice. Hence, most of the computational modeling studies that have examined protein/ice interactions have focused on hydrogen bonding between protein and ice. However, recent mutation studies suggested that HPLC6/ice interaction is not driven by hydrogen bonding, but by van der Waals interactions.; In light of these new experimental results, we wanted to determine whether van der Waals interactions are responsible for the binding specificities of AFPs. To this purpose, computational models of the HPLC6/ice interaction were developed for different ice planes. The results show that the HPLC6 binds in the {lcub}1 1¯ 0 2¯{rcub} direction of the [2 0 2¯ 1] plane, with the Thr-Ala-Asx surface comprising the protein's ice binding face. The binding of HPLC6 to this ice plane is highly preferred, but the protein also binds favorably to the [1 0 1¯ 0] plane using a different Thr-Ala-Ala protein surface. The results show that while van der Waals interactions account for >80% of the intermolecular energy, they are not sufficient to completely explain the AFP binding specificity.; In order to study and characterize the protein at the ice/water interface we computationally modeled a more realistic system involving water, HPLC6 and ice without any constraints. The results from this study show that the ice/water interfacial region is ∼15 Å thick. Furthermore, HPLC6 forms hydrogen bonds with the water molecules in this region. However, there is no significant gain of hydrogen bonds for protein in the interfacial region compared to the solvent water. These results support the hypothesis that hydrogen bonding is not the primary force responsible for interaction of HPLC6 with the water molecules in the ice/water interfacial region.