The Flory isolated-pair hypothesis is not valid for polypeptide chains: implications for protein folding.
Using an all-atom representation, we exhaustively enumerate all sterically allowed conformations for short polyalanyl chains. Only intrachain interactions are considered, including one adjustable parameter, a favorable backbone energy (e.g., a peptide hydrogen bond). The counting is used to reevaluate Flory's isolated-pair hypothesis, the simplifying assumption that each phi,psi pair is sterically independent. This hypothesis is a conceptual linchpin in helix-coil theories and protein folding. Contrary to the hypothesis, we find that systematic local steric effects can extend beyond nearest-chain neighbors and can restrict the size of accessible conformational space significantly. As a result, the entropy price that must be paid to adopt any specific conformation is far less than previously thought.
Pappu
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Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205-2185, USA.
Srinivasan
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Rose
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GD
D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary
D010455:Peptides; C019529:polyalanine