ArticleMolecular biology and evolution2021
Substitutions at Nonconserved Rheostat Positions Modulate Function by Rewiring Long-Range, Dynamic Interactions.
Article in Molecular biology and evolution, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 45 citations in OpenAlex.
- Protein rheostasis: quality control in metastable proteomes.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Distinct energetic blueprints diversify function of conserved protein folds.Nature chemistry · 2026Article
- Expanding the toolkit of LacI/GalR chimeras.PloS one · 2026Article
- Amino acid substitutions at rheostat positions in the NaProtein science : a publication of the Protein Society · 2025Article
- Second-order allosteric control as a mechanism for compensatory mutations in B-cell translocation gene 2.Protein science : a publication of the Protein Society · 2025Article
- Physiological cost of antibiotic resistance: Insights from a ribosome variant in bacteria.Science advances · 2024Article
- Dynamics-based protein network features accurately discriminate neutral and rheostat positions.Biophysical journal · 2024Article
- Dissecting Allosteric Mutations for Antibiotic Resistance by Time-Dependent Linear Response Theory.Journal of chemical theory and computation · 2024Article
- Rheostatic contributions to protein stability can obscure a position's functional role.Protein science : a publication of the Protein Society · 2024Article
- Article
- Article
- Rheostats, toggles, and neutrals, Oh my! A new framework for understanding how amino acid changes modulate protein function.The Journal of biological chemistry · 2024Review
- The intrinsically disordered transcriptional activation domain of CIITA is functionally tuneable by single substitutions: An exception or a new paradigm?Protein science : a publication of the Protein Society · 2024Article
- Active and machine learning-enhanced discovery of new FGFR3 inhibitor, Rhapontin, through virtual screening of receptor structures and anti-cancer activity assessment.Frontiers in molecular biosciences · 2024Article
- In silico discovery of potential PPI inhibitors for anti-lung cancer activity by targeting the CCND1-CDK4 complex via the P21 inhibition mechanism.Frontiers in chemistry · 2024Article
- Simulated pressure changes in LacI suggest a link between hydration and functional conformational changes.Biophysical chemistry · 2024Article
- Engineering gain-of-function mutants of a WW domain by dynamics and structural analysis.Protein science : a publication of the Protein Society · 2023Article
- Allosteric regulatory control in dihydrofolate reductase is revealed by dynamic asymmetry.Protein science : a publication of the Protein Society · 2023Article
- Protein dynamics provide mechanistic insights about epistasis among common missense polymorphisms.Biophysical journal · 2023Article
- TReSR: A PCR-compatible DNA sequence design method for engineering proteins containing tandem repeats.PloS one · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Amino acid substitutions at nonconserved protein positions can have noncanonical and "long-distance" outcomes on protein function. Such outcomes might arise from changes in the internal protein communication network, which is often accompanied by changes in structural flexibility. To test this, we calculated flexibilities and dynamic coupling for positions in the linker region of the lactose repressor protein. This region contains nonconserved positions for which substitutions alter DNA-binding affinity. We first chose to study 11 substitutions at position 52. In computations, substitutions showed long-range effects on flexibilities of DNA-binding positions, and the degree of flexibility change correlated with experimentally measured changes in DNA binding. Substitutions also altered dynamic coupling to DNA-binding positions in a manner that captured other experimentally determined functional changes. Next, we broadened calculations to consider the dynamic coupling between 17 linker positions and the DNA-binding domain. Experimentally, these linker positions exhibited a wide range of substitution outcomes: Four conserved positions tolerated hardly any substitutions ("toggle"), ten nonconserved positions showed progressive changes from a range of substitutions ("rheostat"), and three nonconserved positions tolerated almost all substitutions ("neutral"). In computations with wild-type lactose repressor protein, the dynamic couplings between the DNA-binding domain and these linker positions showed varied degrees of asymmetry that correlated with the observed toggle/rheostat/neutral substitution outcomes. Thus, we propose that long-range and noncanonical substitutions outcomes at nonconserved positions arise from rewiring long-range communication among functionally important positions. Such calculations might enable predictions for substitution outcomes at a range of nonconserved positions.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.