The DOI matches its Crossref record; 112 of the 112 references it cites were found in a registry or an index.
The Role of Conformational Dynamics and Allostery in Modulating Protein Evolution
Abstract
Advances in sequencing techniques and statistical methods have made it possible not only to predict sequences of ancestral proteins but also to identify thousands of mutations in the human exome, some of which are disease associated. These developments have motivated numerous theories and raised many questions regarding the fundamental principles behind protein evolution, which have been traditionally investigated horizontally using the tip of the phylogenetic tree through comparative studies of extant proteins within a family. In this article, we review a vertical comparison of the modern and resurrected ancestral proteins. We focus mainly on the dynamical properties responsible for a protein's ability to adapt new functions in response to environmental changes. Using the Dynamic Flexibility Index and the Dynamic Coupling Index to quantify the relative flexibility and dynamic coupling at a site-specific, single-amino-acid level, we provide evidence that the migration of hinges, which are often functionally critical rigid sites, is a mechanism through which proteins can rapidly evolve. Additionally, we show that disease-associated mutations in proteins often result in flexibility changes even at positions distal from mutational sites, particularly in the modulation of active site dynamics.
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“AlphaFold, which predicts single ranked structures for a protein sequence, is unable to address directly allosteric mechanisms, which are based on the populations of conformational states in the ensembles.”
From AlphaFold, Artificial Intelligence (AI), and Allostery (2022) · cites this paper as [102]
Citations
Cites
Molecular Evolution and Phylogenetics
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“It is known that disease-associated variants alter the stability of a protein (3, 27, 111).”
BackgroundDarwinian Evolution Can Follow Only Very Few Mutational Paths to Fitter Proteins
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Cited by
Sorted by citations
Modeling conformational states of proteins with AlphaFold
Sala, D., Engelberger, F., Mchaourab, H. S., & Meiler, J. (2023) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2023.102645 · Cited by 182
AlphaFold, Artificial Intelligence (AI), and Allostery
Nussinov, R., Zhang, M., Liu, Y., & Jang, H. (2022) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.2c04346 · Cited by 190
RING 3.0: fast generation of probabilistic residue interaction networks from structural ensembles
Clementel, D., Conte, A. D., Monzón, A. M., Camagni, G. F., Minervini, G., Piovesan, D., & Tosatto, S. C. E. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac365 · Cited by 175
The challenge of predicting distal active site mutations in computational enzyme design
Osuna, S. (2020) · Wiley Interdisciplinary Reviews Computational Molecular Science · doi:10.1002/wcms.1502 · Cited by 166
Loop dynamics and the evolution of enzyme activity
Corbella, M., Pinto, G., & Kamerlin, S. C. L. (2023) · Nature Reviews Chemistry · doi:10.1038/s41570-023-00495-w · Cited by 159
Metadata
- Authors
- Campitelli, P., Modi, T., Kumar, S., & Ozkan, S. B.
- Affiliations
- Arizona State University (US)
- King Abdulaziz University (SA)
- Venue
- Annual Review of Biophysics
- Publisher
- Annual Reviews
- Published
- 2020-05-06
- Volume
- 49
- Issue
- 1
- Pages
- 267-288
- ISSN
- 1936-122X (ISSN-L)
- 1936-1238
- OpenAlex
- W3007324177
- Cited by
- 190
- References
- 112
- Citations by year
- 2026: 17 · 2025: 40 · 2024: 31 · 2023: 31 · 2022: 28 · 2021: 32 · 2020: 11
- FWCI
- 2.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Biophysics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- protein evolution, conformational dynamics, allosteric regulation, ancestral proteins, disease-associated mutations, active site dynamics, protein flexibility, functional adaptation
- MeSH terms
- Allosteric Regulation, Humans, Mutation, Protein Conformation, Proteins, Evolution, Molecular
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