Polypeptide helical design

These results indicate that is it possible to change the fold of a protein by changing a restricted set of residues. They also confirm the validity of the rules for stability of helical folds that have been obtained by analysis of experimentally determined protein structures. One obvious impliction of this work is that it might be possible, by just changing a few residues in Janus, to design a mutant that flip-flops between a helical and p sheet structures. Such a polypeptide would be a very interesting model system for prions and other amyloid proteins. 

This review describes designed and folded helical proteins, )5-sheet proteins, a )5)5a-motif and TASP proteins that are targets for functionalization. The functionalization of folded polypeptides using natural amino acids to form catalysts... 

The average conformation of an a-helix-forming polypeptide was formulated first by Zimm and Bragg (4) and then by several authors (5-9). A comprehensive survey of these theories can be found in a book by Poland and Scheraga 10) or in our companion review article (//). In this section, we outline the formulation of Nagai (5). For convenience of presentation, a peptide residue (-CO-HC R-NH-) is called helix unit when distorted to the a-helical conformation, while it is called random-coil unit when allowed to rotate about the bonds C C and C -N. These units are designated h and c. Thus a particular conformation of an a-helix-forming polypeptide chain is represented by a sequence of h and c. 

In the limit of N- oo, Eq. (B-8) reduces to fN = f(2t). Hence /(2t) represents the helical fraction of an infinitely long polypeptide chain. In the ensuing presentation, this is simply designated by /, i.e. 

Scheme 2 shows a cross-sectional representation of a two-stranded a-helical coiled coil of 35 residues per polypeptide chain. The design of this idealized coiled coil incorporated the factors that maximize coiled-coil stability, for example, the hydrophobicity and packing effects in the hydrophobic core, intrachain electrostatic attractions, helical propensity contribution s[2324 from residues outside of the hydrophobic interface, and interchain electrostatic interactions.125 ... 

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