TOWARDS MEETING THE PARACELSUS CHALLENGE - THE DESIGN, SYNTHESIS, ANDCHARACTERIZATION OF PARACELSIN-43, AN ALPHA-HELICAL PROTEIN WITH OVER50-PERCENT SEQUENCE IDENTITY TO AN ALL-BETA PROTEIN
Dt. Jones et al., TOWARDS MEETING THE PARACELSUS CHALLENGE - THE DESIGN, SYNTHESIS, ANDCHARACTERIZATION OF PARACELSIN-43, AN ALPHA-HELICAL PROTEIN WITH OVER50-PERCENT SEQUENCE IDENTITY TO AN ALL-BETA PROTEIN, Proteins, 24(4), 1996, pp. 502-513
In response to the Paracelsus Challenge (Rose and Creamer, Proteins, 1
9:1-3, 1994), we present here the design, synthesis, and characterizat
ion of a helical protein, whose sequence is 50% identical to that of a
n all-beta protein. The new sequence was derived by applying an invers
e protein folding approach, in which the sequence was optimized to ''f
it'' the new helical structure, but constrained to retain 50% of the o
riginal amino acid residues, The program utilizes a genetic algorithm
to optimize the sequence, together with empirical potentials of mean f
orce to evaluate the sequence structure compatibility, Although the de
signed sequence has little ordered (secondary) structure in water, cir
cular dichroism and nuclear magnetic resonance data show clear evidenc
e for significant helical content in water/ethylene glycol and in wate
r/methanol mixtures at low temperatures, as well as melting behavior i
ndicative of cooperative folding, We believe that this represents a si
gnificant step toward meeting the Paracelsus Challenge. (C) 1996 Wiley
-Liss, Inc.