Describing sequence–ensemble relationships for intrinsically disordered proteins
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Intrinsically disordered proteins participate in important protein-protein and protein-nucleic acid interactions and control cellular phenotypes through their prominence as dynamic organizers of transcriptional, post-transcriptional and signalling networks. These proteins challenge the tenets of the structure-function paradigm and their functional mechanisms remain a mystery given that they fail to fold autonomously into specific structures. Solving this mystery requires a first principles understanding of the quantitative relationships between information encoded in the sequences of disordered proteins and the ensemble of conformations they sample. Advances in quantifying sequence-ensemble relationships have been facilitated through a four-way synergy between bioinformatics, biophysical experiments, computer simulations and polymer physics theories. In the present review we evaluate these advances and the resultant insights that allow us to develop a concise quantitative framework for describing the sequence-ensemble relationships of intrinsically disordered proteins.
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In addition to being sequence-specific, the features of conformational ensembles can only be described in terms of single- or multi-parameter distribution functions and/or moments of these distributions.
“in addition to being sequence-specific, the features of conformational ensembles can only be described in terms of single-or multi-parameter distribution functions and/or moments of these distributions.79”
From AlphaFold and Implications for Intrinsically Disordered Proteins (2021) · cites this paper as [79]
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“To date, various studies have assessed the sequence-encoded conformational preferences of IDPs, using concepts from polymer physics reviewed in Mao et al. (2013) and by combining several biophysical techniques with molecular simulations.”
BackgroundControlling entropy to tune the functions of intrinsically disordered regions
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Self-citationTargeting intrinsically disordered proteins in rational drug discovery
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- Authors
- Mao, A. H., Lyle, N., & Pappu, R. V.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Pappu, Rohit V.
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 2012-12-14
- Volume
- 449
- Issue
- 2
- Pages
- 307-318
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC4074364
- OpenAlex
- W2079994402
- Cited by
- 135
- References
- 191
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 13 · 2023: 12 · 2022: 9 · 2021: 10 · 2020: 11 · 2019: 10 · 2018: 12 · 2017: 9 · 2016: 5 · 2015: 8 · 2014: 13 · 2013: 12
- FWCI
- 0.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biochemical Journal (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Science Foundation
- Foundation for the National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R01NS056114)
- 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 › Chemistry › Physical and Theoretical Chemistry › Advanced Physical and Chemical Molecular Interactions
- Keywords
- intrinsically disordered proteins, conformational ensembles, protein conformational dynamics, structure-function relationship, protein-protein interaction, protein-nucleic acid interactions, polymer physics, quantitative framework
- MeSH terms
- Binding Sites, Models, Molecular, Peptides, Protein Binding, Protein Conformation, Proteins, Solvents, Thermodynamics, Protein Structure, Tertiary, Protein Folding
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