title: The Flory isolated-pair hypothesis is not valid for polypeptide chains: implications for protein folding.
abstract: 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.
authors.affiliation: Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205-2185, USA.
authors.forename: R V
authors.initials: RV
authors.lastname: Pappu
authors.forename: R
authors.initials: R
authors.lastname: Srinivasan
authors.forename: G D
authors.initials: GD
authors.lastname: Rose
mesh_terms: D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary
chemical_list: D010455:Peptides; C019529:polyalanine