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Mechanism-based protein design: Attempted "nucleation-condensation" approach to a possible minimal helix-bundle protein

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Title Mechanism-based protein design: Attempted "nucleation-condensation" approach to a possible minimal helix-bundle protein
 
Creator MOHANRAJA, K
DHANASEKARAN, M
KUNDU, B
DURANI, S
 
Subject de-novo design
beta-turns
biological macromolecules
circular-dichroism
transition-states
aqueous-solution
hairpin peptide
conformation
trifluoroethanol
model
de novo design
beta-turn
d-chiral residue
folding nucleation
helix bundle
tertiary structure
conformation energy calculation
 
Description In an intended mechanism-based de novo approach, a 22-mer peptide was so designed as to make it both a stereochemically nucleatable and hydrophobically condensable minimal globular protein. Framework-like nucleation of a triple-helix bundle was targeted by employing as folding nucleators composite beta-turns that could both nucleate helices and place them in close juxtaposition for possible interhelical interaction. To promote the targeted triple-helix bundle to condense as a globular protein, an amphipathic sequence pattern was adopted for possible hydrophobic interhelical interaction. A predominantly helicogenic 22-mer amphipathic peptide was thus designed, punctuating it with composite type II'-III and type II-Asx type beta-turns as the helix nucleators cum chain reversal elements. The peptide made by solid-phase synthesis was shown by NMR and CD to be a nascent and distorted triple-helix bundle in a trifluoroethanol (TFE)-water mixture, but more or less a random coil in water. A fold nucleation effect is evident in the TFE-water mixture, but apparently the hydrophobic effect cannot sustain the peptide conformational order in water. A lack of synergy between folding nucleation and hydrophobic condensation of the peptide is possible. Indeed, a mismatch between the sequential H, P pattern of the peptide and its nascent-type globular fold in a TFE-water mixture is evident based on a simulated annealing study guided by NMR. (C) 2003 .
 
Publisher JOHN WILEY & SONS INC
 
Date 2011-08-16T08:56:38Z
2011-12-26T12:54:51Z
2011-12-27T05:43:11Z
2011-08-16T08:56:38Z
2011-12-26T12:54:51Z
2011-12-27T05:43:11Z
2003
 
Type Article
 
Identifier BIOPOLYMERS, 70(3), 355-363
0006-3525
http://dx.doi.org/10.1002/bip.10465
http://dspace.library.iitb.ac.in/xmlui/handle/10054/9449
http://hdl.handle.net/10054/9449
 
Language en