We present a proposition, the 'poly(L-alanine) hypothesis,' which asserts that the native backbone geometry for any polypeptide or protein of M residues has a closely mimicking, mechanically stable, image in poly(L- alanine) of the same number of residues. Using a molecular mechanics force field to represent the relevant potential energy hypersurfaces, we have carried out calculations over a wide range of M values to show that poly(L- alanine) possesses the structural versatility necessary to satisfy the proposition. These include poly(L-alanine) representatives of minima corresponding to secondary and supersecondary structures, as well as poly(L- alanine) images for tertiary structures of the naturally occurring proteins bovine pancreatic trypsin inhibitor, crambin, ribonuclease A, and superoxide dismutase. The successful validation of the hypothesis presented in this paper indicates that poly(L-alanine) will serve as a good reference material in thermodynamic perturbation theory and calculations aimed at evaluating relative free energies for competing candidate tertiary structures in real polypeptides and proteins.
|Original language||English (US)|
|Number of pages||5|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - 1992|
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