ArticleNature communications2021
Coevolutionary methods enable robust design of modular repressors by reestablishing intra-protein interactions.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- Engineered probiotics block arsenite absorption in the gastrointestinal tract.Trends in biotechnology · 2026Article
- Identification and engineering of highly functional potyviral proteases in cells using co-evolutionary models.Nature communications · 2026Article
- Engineered probiotics that sequester arsenite in a mouse gastrointestinal system.bioRxiv : the preprint server for biology · 2026Article
- Designing modular genetic sensors with TtgR/AcrR family transcriptional regulators by using a statistical and data-driven approach.Nucleic acids research · 2025Article
- Programming Nutrient Detection with Modular Regulators for Dynamic Control of Microbial Biosynthesis.ACS synthetic biology · 2025Article
- Article
- Sequence-Based Protein Design: A Review of Using Statistical Models to Characterize Coevolutionary Traits for Developing Hybrid Proteins as Genetic Sensors.International journal of molecular sciences · 2024Review
- Machine learning in biological physics: From biomolecular prediction to design.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Simultaneous enhancement of multiple functional properties using evolution-informed protein design.Nature communications · 2024Article
- Engineering Proteins Using Statistical Models of Coevolutionary Sequence Information.Cold Spring Harbor perspectives in biology · 2024Review
- Coevolutionary Information Captures Catalytic Functions and Reveals Divergent Roles of Terpene Synthase Interdomain Connections.Biochemistry · 2024Article
- In vivo functional phenotypes from a computational epistatic model of evolution.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Engineering gain-of-function mutants of a WW domain by dynamics and structural analysis.Protein science : a publication of the Protein Society · 2023Article
- Latent generative landscapes as maps of functional diversity in protein sequence space.Nature communications · 2023Article
- Ligand-specific changes in conformational flexibility mediate long-range allostery in the lac repressor.Nature communications · 2023Article
- Computational compensatory mutation discovery approach: Predicting a PARP1 variant rescue mutation.Biophysical journal · 2022Article
- Evolution and folding of repeat proteins.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Deciphering polymorphism in 61,157 Escherichia coli genomes via epistatic sequence landscapes.Nature communications · 2022Article
- Characterizing the landscape of evolvability.Nature ecology & evolution · 2022Article
- Co-evolution of interacting proteins through non-contacting and non-specific mutations.Nature ecology & evolution · 2022Article
Corrections and comments
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Authors and funding
4 authors at 4 institutions in 1 country.
Funding
Abstract
Genetic sensors with unique combinations of DNA recognition and allosteric response can be created by hybridizing DNA-binding modules (DBMs) and ligand-binding modules (LBMs) from distinct transcriptional repressors. This module swapping approach is limited by incompatibility between DBMs and LBMs from different proteins, due to the loss of critical module-module interactions after hybridization. We determine a design strategy for restoring key interactions between DBMs and LBMs by using a computational model informed by coevolutionary traits in the LacI family. This model predicts the influence of proposed mutations on protein structure and function, quantifying the feasibility of each mutation for rescuing hybrid repressors. We accurately predict which hybrid repressors can be rescued by mutating residues to reinstall relevant module-module interactions. Experimental results confirm that dynamic ranges of gene expression induction were improved significantly in these mutants. This approach enhances the molecular and mechanistic understanding of LacI family proteins, and advances the ability to design modular genetic parts.
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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.