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Science 10 December 1993:
Vol. 262. no. 5140, pp. 1680 - 1685
DOI: 10.1126/science.8259512
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Articles

Science, Vol 262, Issue 5140, 1680-1685
Copyright © 1993 by American Association for the Advancement of Science

articles

Protein design by binary patterning of polar and nonpolar amino acids

S Kamtekar, JM Schiffer, H Xiong, JM Babik, and MH Hecht

Department of Chemistry, Princeton University, NJ 08544.

A general strategy is described for the de novo design of proteins. In this strategy the sequence locations of hydrophobic and hydrophilic residues were specified explicitly, but the precise identities of the side 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 proteins. Each gene encoded a different amino acid sequence, but all sequences shared the same pattern of polar and nonpolar residues. Characterization of the expressed proteins indicated that most of the designed sequences folded into compact alpha-helical structures. Thus, a simple binary code of polar and nonpolar residues arranged in the appropriate order can drive polypeptide chains to collapse into globular alpha-helical folds.


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Science. ISSN 0036-8075 (print), 1095-9203 (online)