The Flory isolated-pair hypothesis is not valid for polypeptide chains: Implications for protein folding

Rohit V. Pappu, Rajgopal Srinivasan, George D Rose

Research output: Contribution to journalArticle

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 φ,ψ 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.

Original languageEnglish (US)
Pages (from-to)12565-12570
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number23
DOIs
StatePublished - Nov 7 2000

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Protein Folding
Entropy
Hydrogen
Peptides

Keywords

  • Helix-coil theory
  • Levinthal paradox

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

The Flory isolated-pair hypothesis is not valid for polypeptide chains : Implications for protein folding. / Pappu, Rohit V.; Srinivasan, Rajgopal; Rose, George D.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 97, No. 23, 07.11.2000, p. 12565-12570.

Research output: Contribution to journalArticle

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