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

Citation
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
Citations number
40
Categorie Soggetti
Biology
Journal title
ISSN journal
08873585
Volume
24
Issue
4
Year of publication
1996
Pages
502 - 513
Database
ISI
SICI code
0887-3585(1996)24:4<502:TMTPC->2.0.ZU;2-I
Abstract
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.