Mechanism of action of antifreeze polypeptide HPLC6 in solution: analysis of solvent behaviour by molecular dynamics

Abstract The behaviour of the water surrounding the winter flounder antifreeze protein HPLC6 has been investigated using molecular dynamics with subsequent analysis of the trajectories. Two simulations were carried out: one at room temperature for comparison with pure (TIP3P) water and another at the temperature taken to represent the freezing point of TIP3P water. The peptide was found to remain in a helical conformation with the sidechains of the residues Thr2, Thr13, Thr24, and Thr35 roughly collinear and equally spaced. Furthermore, the structure of the water around these residues appeared to be much better defined than on the opposite face of the helix: this is predominatly hydrophobic. Comparison of the structure and dynamics of the water in the two environments serves to corroborate previously proposed ideas about the mode of antifreeze action. It would appear that the peptide inhibits ice-crystal growth by binding into the surface of trhe crystal via the polar residues, while the apolar residues restrict the binding of further water molecules and keep them in a flux, thus preventing further growth.