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Published June 1997 | public
Journal Article

Automated design of the surface positions of protein helices


Using a protein design algorithm that quantitatively considers side-chain interactions, the design of surface residues of alpha helices was examined. Three scoring functions were tested: a hydrogen-bond potential, a hydrogen-bond potential in conjunction with a penalty for uncompensated burial of polar hydrogens, and a hydrogen-bond potential in combination with helix propensity. The solvent exposed residues of a homodimeric coiled coil based on GCN4-p1 were designed by using the Dead-End Elimination Theorem to find the optimal amino acid sequence for each scoring function. The corresponding peptides were synthesized and characterized by circular dichroism spectroscopy and size exclusion chromatography. The designed peptides were dimeric and nearly 100% helical at 1 °C, with melting temperatures from 69-72 °C, over 12 °C higher than GCN4-p1, whereas a random hydrophilic sequence at the surface positions produced a peptide that melted at 15 °C. Analysis of the designed sequences suggests that helix propensity is the key factor in sequence design for surface helical positions.

Additional Information

© 1997 The Protein Society. Received January 13, 1997; Accepted March 11, 1997. Article first published online: 31 Dec. 2008. We wish to thank G. Hathaway and D. Krapf of the Caltech Protein and Peptide Microanalytical Laboratory for mass spectra and amino acid analysis and the Caltech Center for Advanced Computing Research for use of the Intel Delta. This work was supported by the Rita Allen Foundation, the David and Lucile Packard Foundation and the Searle Scholars Program/The Chicago Community Trust. B.I.D. is partially supported by NIH Training Grant GM 08346. D.B.G. is partially supported by NIH Training Grant GM 07616C-19.

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