ISSN:
0887-3585
Keywords:
de novo design
;
protein structure
;
inverse folding
;
genetic algorithms
;
1H NMR
;
CD
;
peptide
;
protein folding
;
methanol
;
ethylene glycol
;
Chemistry
;
Biochemistry and Biotechnology
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Medicine
Notes:
In response to the Paracelsus Challenge (Rose and Creamer, Proteins, 19:1-3, 1994), we present here the design, synthesis, and characterization of a helical protein, whose sequence is 50% identical to that of an all-β protein. The new sequence was derived by applying an inverse protein folding approach, in which the sequence was optimized to “fit” the new helical structure, but constrained to retain 50% of the original amino acid residues. The program utilizes a genetic algorithm to optimize the sequence, together with empirical potentials of mean force to evaluate the sequence-structure compatibility. Although the designed sequence has little ordered (secondary) structure in water, circular dichroism and nuclear magnetic resonance data show clear evidence for significant helical content in water/ethylene glycol and in water/methanol mixtures at low temperatures, as well as melting behavior indicative of cooperative folding. We believe that this represents a significant step toward meeting the Paracelsus Challenge.
Additional Material:
5 Ill.
Type of Medium:
Electronic Resource
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