CRISPR–Cas9 Structures and Mechanisms



Cas9-catalyzed DNA Cleavage Generates Staggered Ends: Evidence from Molecular Dynamics Simulations

Probing the structural dynamics of the CRISPR-Cas9 RNA-guided DNA-cleavage system by coarse-grained modeling

Striking Plasticity of CRISPR-Cas9 and Key Role of Non-target DNA, as Revealed by Molecular Simulations

CRISPR-Cas9 conformational activation as elucidated from enhanced molecular simulations

Experiments with structural & mechanistic focus. 

DNA interrogation by the CRISPR RNA-guided endonuclease Cas9

Massively Parallel Biophysical Analysis of CRISPR-Cas Complexes on Next Generation Sequencing Chips

Cas9 domain fluctuations by FRET

Structures and mechanisms by Cryo-EM Cell 2017

Biophysical models of specificity. 

DNA targeting specificity of RNA-guided Cas9 nucleases ( Contains experimental data about the specificity. They also have a server based on the data.

A Biophysical Model of CRISPR/Cas9 Activity for Rational Design of Genome Editing and Gene Regulation: This is a simple biophysical model used to predict the specificity of the sgRNA based on the sequence. They split the process in 3 steps and add the free energy change of each process to calculate a binding energy.

High-fidelity CRISPR–Cas9 nucleases with no detectable genome-wide off-target effects : Mutations on residues that bind to the phosphate backbone of the DNA can improve the specificity.


QM:MM Simulations

Gamess+Tinker (advantages: free, disadvantages: might not run well )

Gaussian+Gromacs (advantages: will work well, Scuseria will likely help; disadvantages: will likely be limited to Rice U comp. resources.)

Mechanistic Insight into Catalytic Activity of BBA-Metallonucleases (This model system, Vibrio vulnificus, is thought to have the same cleavage mechanism as the HNH domain.)

Catalytic Mechanisms of Restriction and Homing Endonucleases (A general overview of both one- and two-metal reactions, not specifically theory-oriented.)

The Nucleophile in Ribozyme Catalysis (Not directly related, but an analogous cleavage reaction. The SI also has lots of detailed information on their QM/MM simulations.)

RNA coarse grain models:

Layman news:


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