Frustration in biomolecules
Open accessAbstract
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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In solution, protein conformational fluctuations cause even stable proteins to form ensembles of highly populated substates with thermodynamic population distributions.
“Conformational fluctuations of proteins in solution,11 as revealed mostly by nuclear magnetic resonance (NMR) experiments and computations, make even stable proteins exist as conformational ensembles with highly populated substates whose populations follow thermodynamic distributions.12–16”
From Protein Ensembles: How Does Nature Harness Thermodynamic Fluctuations for Life? The Diverse Functional Roles of Conformational Ensembles in the Cell (2016) · cites this paper as [15]
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Self-citation
Flagged first, then by citations
Research works printed but not linked: 3
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Chaperone-Bound Clients: The Importance of Being Dynamic
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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
- Publisher
- Cambridge University Press (CUP)
- Published
- 2014-09-16
- Volume
- 47
- Issue
- 4
- Pages
- 285-363
- ISSN
- 0033-5835 (ISSN-L)
- 1469-8994
- PMC
- PMC4256721
- 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
- bronze
- doi.org
- 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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