Dynamics and mechanisms of CRISPR-Cas9 through the lens of computational methods

Giulia Palermo 
Associate Professor, The University of California Riverside - USA

April 19, 2023 (11:30-12:30)
Webinar Link: https://meet.goto.com/348503085

Abstract: The clustered regularly interspaced short palindromic repeat (CRISPR) genome-editing revolution established the beginning of a new era in life sciences. I will report the role of state-of-the-art computations in the CRISPR-Cas9 revolution, from the early refinement of cryo-EM data to enhanced simulations of large-scale conformational transitions. Molecular simulations reported a mechanism for RNA binding and the formation of a catalytically competent Cas9 enzyme, in agreement with subsequent structural studies. Inspired by single-molecule experiments, molecular dynamics offered a rationale for the onset of off-target effects, while graph theory unveiled the allosteric regulation. Finally, the use of a mixed quantum-classical approach established the catalytic mechanism of DNA cleavage. Overall, molecular simulations have been instrumental in understanding the dynamics and mech- anism of CRISPR-Cas9, contributing to understanding func- tion, catalysis, allostery, and specificity

Author's Info: https://palermolab.com/

Link to video: https://youtu.be/V5k88es8Vtg