MOLECULAR-DYNAMICS SIMULATIONS OF A WINTER FLOUNDER ANTIFREEZE POLYPEPTIDE IN AQUEOUS-SOLUTION

A winter flounder antifreeze polypeptide (HPLC-6) has been studied in vacuo and in aqueous solution using molecular dynamics computer simula tion techniques. The helical conformation of this polypeptide was foun d to be stable both in vacuum and in solution. The major stabilizing i nteractions were found to be the main-chain hydrogen bonds, a salt-bri dge interaction, and solute-solvent hydrogen bonds. A significant bend ing in the middle of the polypeptide chain was observed both in vacuo and in solvent at 300 K. Possible causes of the bending are discussed. From simulations of mutant polypeptide molecules in vacuo, it is conc luded that the bend in the native polypeptide was caused by side chain to backbone hydrogen bond competition involving the Thr 24 side chain and facilitated by strains on the helix resulting from the Lys 18-Glu 22 salt bridge. (C) 1993 John Wiley & Sons, Inc.