Folding funnels and binding mechanisms

Buyong Ma, Sandeep Kumar, Chung Jung Tsai, Ruth Nussinov*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


The long-held views on lock-and-key versus induced fit in binding arose from the notion that a protein exists in a single, most stable conformation, dictated by its sequence. However, in solution proteins exist in a range of conformations, which may be described by statistical mechanical laws and their populations follow statistical distributions. Upon binding, the equilibrium will shift in favor of the bound conformation from the ensemble of conformations around the bottom of the folding funnel. Hence here we extend the implications and the usefulness of the folding funnel concept to explain fundamental binding mechanisms.

Original languageEnglish
Pages (from-to)713-720
Number of pages8
JournalProtein Engineering
Issue number9
StatePublished - 1999


  • Binding
  • Conformational ensembles
  • Energy landscape
  • Folding
  • Funnels
  • Lock-and-key vs induced fit
  • Misfolding


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