ArticleNucleic acids research2009
An affinity-based scoring scheme for predicting DNA-binding activities of modularly assembled zinc-finger proteins.
Article in Nucleic acids research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- DNA recognition, cleavage, and toxic metal ion interaction of an artificial zinc finger protein inside E. coli cells.Protein science : a publication of the Protein Society · 2026Article
- Article
- In Vivo Genome Editing as a Therapeutic Approach.International journal of molecular sciences · 2018Review
- Pathogen-specific DNA sensing with engineered zinc finger proteins immobilized on a polymer chip.The Analyst · 2018Article
- Multiplexed detection of pathogen-specific DNA using engineered zinc finger proteins without target amplification.Analytical methods : advancing methods and applications · 2016Article
- An improved predictive recognition model for Cys(2)-His(2) zinc finger proteins.Nucleic acids research · 2014Article
- Global analysis of Drosophila Cys₂-His₂ zinc finger proteins reveals a multitude of novel recognition motifs and binding determinants.Genome research · 2013Article
- Highly active zinc-finger nucleases by extended modular assembly.Genome research · 2013Article
- A large-scale in vivo analysis reveals that TALENs are significantly more mutagenic than ZFNs generated using context-dependent assembly.Nucleic acids research · 2013Article
- Using defined finger-finger interfaces as units of assembly for constructing zinc-finger nucleases.Nucleic acids research · 2013Article
- Natural zinc ribbon HNH endonucleases and engineered zinc finger nicking endonuclease.Nucleic acids research · 2013Article
- Specific labeling of zinc finger proteins using noncanonical amino acids and copper-free click chemistry.Bioconjugate chemistry · 2012Article
- An optimized two-finger archive for ZFN-mediated gene targeting.Nature methods · 2012Article
- DNA-guided assembly of biosynthetic pathways promotes improved catalytic efficiency.Nucleic acids research · 2012Article
- Evaluation and application of modularly assembled zinc-finger nucleases in zebrafish.Development (Cambridge, England) · 2011Article
- Efficient design and assembly of custom TALEN and other TAL effector-based constructs for DNA targeting.Nucleic acids research · 2011Article
- Sequence specificity is obtained from the majority of modular C2H2 zinc-finger arrays.Nucleic acids research · 2011Article
- Extensive protein and DNA backbone sampling improves structure-based specificity prediction for C2H2 zinc fingers.Nucleic acids research · 2011Article
- A zinc finger protein array for the visual detection of specific DNA sequences for diagnostic applications.Nucleic acids research · 2011Article
- Zinc finger protein-dependent and -independent contributions to the in vivo off-target activity of zinc finger nucleases.Nucleic acids research · 2011Article
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5 authors.
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Abstract
Zinc-finger proteins (ZFPs) have long been recognized for their potential to manipulate genetic information because they can be engineered to bind novel DNA targets. Individual zinc-finger domains (ZFDs) bind specific DNA triplet sequences; their apparent modularity has led some groups to propose methods that allow virtually any desired DNA motif to be targeted in vitro. In practice, however, ZFPs engineered using this 'modular assembly' approach do not always function well in vivo. Here we report a modular assembly scoring strategy that both identifies combinations of modules least likely to function efficiently in vivo and provides accurate estimates of their relative binding affinities in vitro. Predicted binding affinities for 53 'three-finger' ZFPs, computed based on energy contributions of the constituent modules, were highly correlated (r = 0.80) with activity levels measured in bacterial two-hybrid assays. Moreover, K(d) values for seven modularly assembled ZFPs and their intended targets, measured using fluorescence anisotropy, were also highly correlated with predictions (r = 0.91). We propose that success rates for ZFP modular assembly can be significantly improved by exploiting the score-based strategy described here.
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