ArticleNucleic acids research2010
Computational reprogramming of homing endonuclease specificity at multiple adjacent base pairs.
Article in Nucleic acids research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
What it found
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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.
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Who cites it
56 citing papers in PubMed.
- Caveat emptor: predicting and modeling protein-DNA recognition and binding via machine-learning computational approaches.Nucleic acids research · 2026Review
- Manipulation of 7‑Finger Zinc Finger Nuclease Increases the Efficiency of Genome Editing in Human Cells.ACS bio & med chem Au · 2025Article
- Computational design of sequence-specific DNA-binding proteins.Nature structural & molecular biology · 2025Article
- Precise genome editing process and its applications in plants driven by AI.Functional & integrative genomics · 2025Review
- An integrative approach to protein sequence design through multiobjective optimization.PLoS computational biology · 2024Article
- Engineering of Zinc Finger Nucleases Through Structural Modeling Improves Genome Editing Efficiency in Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- An integrative approach to protein sequence design through multiobjective optimization.bioRxiv : the preprint server for biology · 2024Article
- Multiple adaptations underly co-option of a CRISPR surveillance complex for RNA-guided DNA transposition.Molecular cell · 2023Article
- Optimization of Protein Thermostability and Exploitation of Recognition Behavior to Engineer Altered Protein-DNA Recognition.Structure (London, England : 1993) · 2020Article
- Macromolecular modeling and design in Rosetta: recent methods and frameworks.Nature methods · 2020Review
- Understanding the structural details of APOBEC3-DNA interactions using graph-based representations.Current research in structural biology · 2020Article
- Modifying a covarying protein-DNA interaction changes substrate preference of a site-specific endonuclease.Nucleic acids research · 2019Article
- Engineering altered protein-DNA recognition specificity.Nucleic acids research · 2018Review
- Gene Drive for Mosquito Control: Where Did It Come from and Where Are We Headed?International journal of environmental research and public health · 2017Review
- Programmable Genome Editing Tools and their Regulation for Efficient Genome Engineering.Computational and structural biotechnology journal · 2017Review
- Article
- Integrating gene synthesis and microfluidic protein analysis for rapid protein engineering.Nucleic acids research · 2016Article
- Computationally Designed Bispecific Antibodies using Negative State Repertoires.Structure (London, England : 1993) · 2016Article
- Rosetta and the Design of Ligand Binding Sites.Methods in molecular biology (Clifton, N.J.) · 2016Article
- Effects of Non-Natural Amino Acid Incorporation into the Enzyme Core Region on Enzyme Structure and Function.International journal of molecular sciences · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
Site-specific homing endonucleases are capable of inducing gene conversion via homologous recombination. Reprogramming their cleavage specificities allows the targeting of specific biological sites for gene correction or conversion. We used computational protein design to alter the cleavage specificity of I-MsoI for three contiguous base pair substitutions, resulting in an endonuclease whose activity and specificity for its new site rival that of wild-type I-MsoI for the original site. Concerted design for all simultaneous substitutions was more successful than a modular approach against individual substitutions, highlighting the importance of context-dependent redesign and optimization of protein-DNA interactions. We then used computational design based on the crystal structure of the designed complex, which revealed significant unanticipated shifts in DNA conformation, to create an endonuclease that specifically cleaves a site with four contiguous base pair substitutions. Our results demonstrate that specificity switches for multiple concerted base pair substitutions can be computationally designed, and that iteration between design and structure determination provides a route to large scale reprogramming of specificity.
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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.