PROTEIN DESIGN BY BINARY PATTERNING OF POLAR AND NONPOLAR AMINO-ACIDS

A general strategy is described for the de novo design of proteins. In this strategy the sequence locations of hydrophobic and hydrophilic r esidues were specified explicitly, but the precise identities of the s ide chains were not constrained and varied extensively. This strategy was tested by constructing a large collection of synthetic genes whose protein products were designed to fold into four-helix bundle protein s. Each gene encoded a different amino acid sequence, but all sequence s shared the same pattern of polar and nonpolar residues. Characteriza tion of the expressed proteins indicated that most of the designed seq uences folded into compact alpha-helical structures. Thus, a simple bi nary code of polar and nonpolar residues arranged in the appropriate o rder can drive polypeptide chains to collapse into globular alpha-heli cal folds.