Local and non-local native topologies reveal the underlying folding landscape of proteins

Taisong Zou, Sefika Ozkan

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Due to Plaxco, Simons, Baker and others, it is now well known that the two-state single domain protein folding rate is fairly well predicted from knowledge of the topology of the native structure. Plaxco et al found that the folding rates of two-state proteins correlate with the average degree to which native contacts are 'local' within the chain sequence: fast-folders usually have mostly local structures. Here, we dissected the native topology further by focusing on non-local and local contacts using lower and upper bounds of allowable sequence separation in computing the average contact order. We analyzed non-local and local contacts of 82 two-state proteins whose experimental folding rates span over six orders of magnitude. We observed that both the number of non-local contacts and the average sequence separation of non-local contacts (non-local CO) are both negatively correlated with the folding rate, showing that the non-local contacts dominate the barrier-crossing process. Surprisingly, the local contact orders of the proteins also correlate with the folding rates. However, this correlation shows a strong positive trend indicating the role of a diffusive search in the denatured basin.

Original languageEnglish (US)
Article number066011
JournalPhysical biology
Issue number6
StatePublished - Dec 1 2011

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Molecular Biology
  • Cell Biology


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