Cited by 314Protein Structure and DynamicsRNA and protein synthesis mechanismsTheoretical and Computational Physics

Frustration in biomolecules

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Ferreiro, Diego U., Komives, Elizabeth A., Wolynes, Peter G.·2014·Quarterly Reviews of Biophysics

Abstract

Biomolecules are the prime information processing elements of living matter. Most of these inanimate systems are polymers that compute their own structures and dynamics using as input seemingly random character strings of their sequence, following which they coalesce and perform integrated cellular functions. In large computational systems with finite interaction-codes, the appearance of conflicting goals is inevitable. Simple conflicting forces can lead to quite complex structures and behaviors, leading to the concept of frustration in condensed matter. We present here some basic ideas about frustration in biomolecules and how the frustration concept leads to a better appreciation of many aspects of the architecture of biomolecules, and especially how biomolecular structure connects to function by means of localized frustration. These ideas are simultaneously both seductively simple and perilously subtle to grasp completely. The energy landscape theory of protein folding provides a framework for quantifying frustration in large systems and has been implemented at many levels of description. We first review the notion of frustration from the areas of abstract logic and its uses in simple condensed matter systems. We discuss then how the frustration concept applies specifically to heteropolymers, testing folding landscape theory in computer simulations of protein models and in experimentally accessible systems. Studying the aspects of frustration averaged over many proteins provides ways to infer energy functions useful for reliable structure prediction. We discuss how frustration affects folding mechanisms. We review here how the biological functions of proteins are related to subtle local physical frustration effects and how frustration influences the appearance of metastable states, the nature of binding processes, catalysis and allosteric transitions. In this review, we also emphasize that frustration, far from being always a bad thing, is an essential feature of biomolecules that allows dynamics to be harnessed for function. In this way, we hope to illustrate how Frustration is a fundamental concept in molecular biology.

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Research works printed but not linked: 3

  1. Ferreiro Diego U 2008c The energy landscapes of repeat-containing proteins: topology, cooperativity, and the folding funnels of one-dimensional architectures PLoS Comput Biol 4 5 e1000070 10.1371/journal.pcbi.1000070 18483553 PMC2366061 · DOI
  2. Néel L 1970 Magnetism and the local molecular field In Nobel Lectures, vol. Physics 1963–1970 318 341 Amsterdam Elsevier
  3. Wannier GH 1950b Antiferromagnetism. the triangular ising net Physical Review 79 2 357

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Authors
Ferreiro, D. U., Komives, E. A., & Wolynes, P. G.
Affiliations
  • Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
  • University of California San Diego (US)
  • Center for Theoretical Biological Physics (US)
Corresponding author
  • Komives, Elizabeth A.
  • Wolynes, Peter G.
Venue
Quarterly Reviews of Biophysics
Published
2014-09-16
Volume
47
Issue
4
Pages
285-363
ISSN
  • 0033-5835 (ISSN-L)
  • 1469-8994
OpenAlex
W2100139545
Cited by
314
References
248
Citations by year
2026: 25 · 2025: 31 · 2024: 24 · 2023: 24 · 2022: 36 · 2021: 41 · 2020: 24 · 2019: 25 · 2018: 21 · 2017: 22 · 2016: 19 · 2015: 16 · 2014: 5 · 2013: 1
FWCI
1.95
Type
journal article
Language
en
Open access
Locations
  • Quarterly Reviews of Biophysics (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Rice Research Repository (Rice University) (acceptedVersion)
  • Rice Research Repository (Rice University) (submittedVersion)
Funders
  • Rice University
  • Consejo Nacional de Investigaciones Científicas y Técnicas
  • Agencia Nacional de Promoción Científica y Tecnológica (CONICET)
  • National Institute of General Medical Sciences (GM44557, R01 GM44 557, GM 071862, P01GM071862, R01GM044557)
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 › Physics and Astronomy › Condensed Matter Physics › Theoretical and Computational Physics
Keywords
frustration, biomolecules, protein folding, energy landscape theory, heteropolymers, protein structure prediction, folding mechanism, metastable states, protein binding, catalysis, allosteric transition, structure-function relationship, condensed matter physics
MeSH terms
Biochemistry, Biopolymers, Humans, Movement, Thermodynamics, Magnetic Phenomena

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