Molecular Simulations have Boosted Knowledge of CRISPR/Cas9: A Review

Genome editing allows scientists to change an organism’s DNA. One promis-ing genome editing protocol, already validated in living organisms, is basedon clustered regularly interspaced short palindromic repeats (CRISPR)/Casprotein-nucleic acid complexes. When the CRISPR/Cas approach was firstdemonstrated in 2012, its advantages with respect to previously availabletechniques, such as zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), immediately got attention and the methodhas seen a surge of experimental and computational investigations since then.However, the molecular mechanisms involved in target DNA recognition andcleavage are still not completely resolved and need further attention. The largesize and complex nature of CRISPR/Cas9 complexes has been a challengefor computational studies, but some seed results exist and are illuminatingon the cleavage activity. In this short review, we present recent progressin studying CRISPR/Cas9 systems by molecular dynamics simulations withcoarse-grained and atomistic descriptions, including enhanced sampling.