Abstract
We have designed, synthesized, crystallized, and performed x-ray analysis of several hydrophobic tripeptides that show an extended near alpha-helical structure in the crystalline state. All of the tripeptides that show this remarkably stable helix crystallize with two or three water molecules; they all have glycine at the N terminus and have increasing hydrophobicity as one moves from the N to C terminus. Even though three residues in the oligomer are not sufficient to complete a turn, one of the water molecules acts as an added residue and links up adjacent tripeptide segments along the helix axis so that in the crystal, the helix appears effectively as one long continuous helix. Two of these tripeptides are stabilized by two water molecules that enable the peptides to complete a turn of the helix and extend the helical structure throughout the crystal by linking translationally related peptides by hydrogen bonds. In two other peptides, these roles are played by three rather than two water molecules. Though these tripeptides have different crystal symmetry, they all show the basic pattern of hydrated helix and packing, indicating the strong conformational preference for a stable structure even for these tripeptides. Such conformationally stable hydrated structures for short specific related sequences illustrate their possible importance in nucleating protein folding and in the role water molecules play in such events.