Cited by 1,163Protein Structure and DynamicsRNA and protein synthesis mechanismsEnzyme Structure and Function

The Protein Folding Problem

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Dill, Ken A., Ozkan, S. Banu, Shell, M. Scott, Weikl, Thomas R.·2008·Annual Review of Biophysics

Abstract

The "protein folding problem" consists of three closely related puzzles: (a) What is the folding code? (b) What is the folding mechanism? (c) Can we predict the native structure of a protein from its amino acid sequence? Once regarded as a grand challenge, protein folding has seen great progress in recent years. Now, foldable proteins and nonbiological polymers are being designed routinely and moving toward successful applications. The structures of small proteins are now often well predicted by computer methods. And, there is now a testable explanation for how a protein can fold so quickly: A protein solves its large global optimization problem as a series of smaller local optimization problems, growing and assembling the native structure from peptide fragments, local structures first.

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Crossref · 10.1146/annurev.biophys.37.092707.153558

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Research works printed but not linked: 2

  1. [94]Handel T, Degrado WF. Denovo design of a Zn2+-binding protein. J Am Chem Soc. 1990;112:6710–11. [Google Scholar]
  2. [105]Hubner IA, Shimada J, Shakhnovich EI. Φ values and the folding transition state of protein G: utilization and interpretation of experimental data through simulation. Abstr Pap Am Chem Soc. 2003;226:U450. [Google Scholar]

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Authors
Dill, K. A., Ozkan, S. B., Shell, M. S., & Weikl, T. R.
Affiliations
  • University of California, San Francisco (US)
  • Arizona State University (US)
  • University of California, Santa Barbara (US)
  • Max Planck Institute of Colloids and Interfaces (DE)
Venue
Annual Review of Biophysics
Published
2008-06-01
Volume
37
Issue
1
Pages
289-316
ISSN
  • 1936-122X (ISSN-L)
  • 1936-1238
OpenAlex
W2129020329
Cited by
1,163
References
248
Citations by year
2026: 51 · 2025: 61 · 2024: 60 · 2023: 70 · 2022: 73 · 2021: 73 · 2020: 59 · 2019: 53 · 2018: 52 · 2017: 47 · 2016: 48 · 2015: 43 · 2014: 70 · 2013: 82 · 2012: 78
FWCI
6.04
Type
journal article
Language
en
Open access
Locations
  • Annual Review of Biophysics (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Max Planck Institute for Plasma Physics (submittedVersion)
  • Max Planck Digital Library (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
Funders
National Institute of General Medical Sciences (GM34993, R01GM034993)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
Keywords
protein folding, folding mechanism, protein structure prediction, de novo protein design, peptide fragments, local optimization, global optimization, folding rate
MeSH terms
Computer Simulation, Models, Chemical, Models, Molecular, Protein Conformation, Proteins, Protein Folding

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