Molecular simulations have boosted knowledge of CRISPR/Cas9: A Review

TL;DR

This review summarizes recent advances in understanding CRISPR/Cas9 mechanisms through molecular dynamics simulations, highlighting how computational studies have contributed to knowledge of DNA recognition and cleavage.

Contribution

It provides an overview of recent molecular simulation studies on CRISPR/Cas9, emphasizing the role of computational methods in elucidating its molecular mechanisms.

Findings

Molecular dynamics simulations have revealed details of DNA recognition by CRISPR/Cas9.

Enhanced sampling techniques have advanced understanding of Cas9 conformational changes.

Computational studies are overcoming challenges posed by the complex size of CRISPR/Cas9.

Abstract

Genome editing allows scientists to change an organism's DNA. One promising genome editing protocol, already validated in living organisms, is based on clustered regularly interspaced short palindromic repeats (CRISPR)/Cas protein-nucleic acid complexes. When the CRISPR/Cas approach was first demonstrated in 2012, its advantages with respect to previously available techniques, such as zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), immediately got attention and the method has seen a surge of experimental and computational investigations since then. However, the molecular mechanisms involved in target DNA recognition and cleavage are still not completely resolved and need further attention. The large size and complex nature of CRISPR/Cas9 complexes has been a challenge for computational studies, but some seed results exist and are illuminating on the cleavage activity. In this short review, we present recent progress in studying CRISPR/Cas9 systems by molecular dynamics simulations with coarse-grained and atomistic descriptions, including enhanced sampling.