Deciphering the QR Code of the CRISPR-Cas9 System: Synergy between Gln768 (Q) and Arg976 (R).

ABSTRACT: Markov state models (MSMs) and machine learning (ML) algorithms can extrapolate the long-time-scale behavior of large biomolecules from molecular dynamics (MD) trajectories. In this study, an MD-MSM-ML scheme has been applied to probe the large endonuclease (Cas9) in the bacterial adaptive immunity CRISPR-Cas9 system. CRISPR has become a programmable and state-of-the-art powerful genome editing tool that has already revolutionized life sciences. CRISPR-Cas9 is programmed to process specific DNA sequences in the genome. However, human/biomedical applications are compromised by off-target DNA damage. Characterization of Cas9 at the structural and biophysical levels is a prerequisite for the development of efficient and high-fidelity Cas9 variants. The Cas9 wild type and two variants (R63A-R6

SUBMITTER: Daskalakis V 

PROVIDER: S-EPMC9955204 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature