ArticleACS central science2016
Striking Plasticity of CRISPR-Cas9 and Key Role of Non-target DNA, as Revealed by Molecular Simulations.
Article in ACS central science, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 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.
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Who cites it
81 citing papers in PubMed, 143 citations in OpenAlex.
- A dynamically frustrated allosteric checkpoint consistent with conformational proofreading in CRISPR-Cas9.Nucleic acids research · 2026Article
- CRISPR RNA architecture steers Cas9 catalysis and fidelity via a guide repeat clasp motif.Nucleic acids research · 2026Article
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- Investigating the molecular mechanisms underlying the anti-CRISPR function of AcrIIA13b protein.The FEBS journal · 2026Article
- AcrIIA7 hijacks tracrRNA to block CRISPR-Cas system.Nature communications · 2026Article
- A Computational Model for Nme1Cas9 HNH Activation Driven by Dynamic Interface Engineering at Residues S593 and W596.Biomolecules · 2026Article
- Exploring the temperature stability of CRISPR-Cas12b using molecular dynamics simulations.Molecular systems design & engineering · 2026Article
- Computation and deep-learning-driven advances in CRISPR genome editing.Nature structural & molecular biology · 2026Review
- Characterization and modulation of human insulin degrading enzyme conformational dynamics to control enzyme activity.bioRxiv : the preprint server for biology · 2025Article
- A guide RNA repeat checkpoint steers CRISPR-Cas9 catalysis.bioRxiv : the preprint server for biology · 2025Article
- Design Rules for Expanding PAM Compatibility in CRISPR-Cas9 from the VQR, VRER and EQR variants.bioRxiv : the preprint server for biology · 2025Article
- Learning to utilize internal protein 3D nanoenvironment descriptors in predicting CRISPR-Cas9 off-target activity.NAR genomics and bioinformatics · 2025Article
- Article
- Exploring CRISPR-Cas9 HNH-Domain-Catalyzed DNA Cleavage Using Accelerated Quantum Mechanical Molecular Mechanical Free Energy Simulation.Biochemistry · 2025Article
- Structural basis of Cas9 DNA interrogation with a 5' truncated sgRNA.Nucleic acids research · 2025Article
- Graph theory approaches for molecular dynamics simulations.Quarterly reviews of biophysics · 2024Article
- Conformational plasticity of SpyCas9 induced by AcrIIA4 and AcrIIA2: Insights from molecular dynamics simulation.Computational and structural biotechnology journal · 2024Article
- Comprehensive Assessment of Force-Field Performance in Molecular Dynamics Simulations of DNA/RNA Hybrid Duplexes.Journal of chemical theory and computation · 2024Article
- AcrIIA28 is a metalloprotein that specifically inhibits targeted-DNA loading to SpyCas9 by binding to the REC3 domain.Nucleic acids research · 2024Article
- High-fidelity, hyper-accurate, and evolved mutants rewire atomic-level communication in CRISPR-Cas9.Science advances · 2024Article
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
The CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 system recently emerged as a transformative genome-editing technology that is innovating basic bioscience and applied medicine and biotechnology. The endonuclease Cas9 associates with a guide RNA to match and cleave complementary sequences in double stranded DNA, forming an RNA:DNA hybrid and a displaced non-target DNA strand. Although extensive structural studies are ongoing, the conformational dynamics of Cas9 and its interplay with the nucleic acids during association and DNA cleavage are largely unclear. Here, by employing multi-microsecond time scale molecular dynamics, we reveal the conformational plasticity of Cas9 and identify key determinants that allow its large-scale conformational changes during nucleic acid binding and processing. We show how the "closure" of the protein, which accompanies nucleic acid binding, fundamentally relies on highly coupled and specific motions of the protein domains, collectively initiating the prominent conformational changes needed for nucleic acid association. We further reveal a key role of the non-target DNA during the process of activation of the nuclease HNH domain, showing how the nontarget DNA positioning triggers local conformational changes that favor the formation of a catalytically competent Cas9. Finally, a remarkable conformational plasticity is identified as an intrinsic property of the HNH domain, constituting a necessary element that allows for the HNH repositioning. These novel findings constitute a reference for future experimental studies aimed at a full characterization of the dynamic features of the CRISPR-Cas9 system, and-more importantly-call for novel structure engineering efforts that are of fundamental importance for the rational design of new genome-engineering applications.
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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.