Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 1997 Jan;4(1):10-9.
doi: 10.1038/nsb0197-10.

From Levinthal to pathways to funnels

K A Dill  1 , H S Chan
Affiliations
Review

From Levinthal to pathways to funnels

K A Dill et al. Nat Struct Biol. 1997 Jan.

Abstract

While the classical view of protein folding kinetics relies on phenomenological models, and regards folding intermediates in a structural way, the new view emphasizes the ensemble nature of protein conformations. Although folding has sometimes been regarded as a linear sequence of events, the new view sees folding as parallel microscopic multi-pathway diffusion-like processes. While the classical view invoked pathways to solve the problem of searching for the needle in the haystack, the pathway idea was then seen as conflicting with Anfinsen's experiments showing that folding is pathway-independent (Levinthal's paradox). In contrast, the new view sees no inherent paradox because it eliminates the pathway idea: folding can funnel to a single stable state by multiple routes in conformational space. The general energy landscape picture provides a conceptual framework for understanding both two-state and multi-state folding kinetics. Better tests of these ideas will come when new experiments become available for measuring not just averages of structural observables, but also correlations among their fluctuations. At that point we hope to learn much more about the real shapes of protein folding landscapes.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

LinkOut - more resources