Protein folding: Could hydrophobic collapse be coupled with hydrogen-bond formation?

Ariel Fernández, József Kardos, Yuji Goto

Research output: Contribution to journalArticle

40 Citations (Scopus)


A judicious examination of an exhaustive PDB sample of soluble globular proteins of moderate size (N<102) reveals a commensurable relationship between hydrophobic surface burial and number of backbone hydrogen bonds. An analysis of 50 000 conformations along the longest all-atom MD trajectory allows us to infer that not only the hydrophobic collapse is concurrent with the formation of backbone amide-carbonyl hydrogen bonds, they are also dynamically coupled processes. In statistical terms, hydrophobic clustering of the side chains is inevitably conducive to backbone burial and the latter process becomes thermodynamically too costly and kinetically unfeasible without amide-carbonyl hydrogen-bond formation. Furthermore, the desolvation of most hydrogen bonds is exhaustive along the pathway, implying that such bonds guide the collapse process.

Original languageEnglish
Pages (from-to)187-192
Number of pages6
JournalFEBS letters
Issue number1-3
Publication statusPublished - Feb 11 2003



  • Hydrogen bonds
  • Hydrophobic collapse
  • Protein folding
  • Statistical mechanics

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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