Prof. Giulia Palermo
Physical, Physical Chemistry Seminar
Professor at the University of California, Riverside
Department of Bioengineering and Chemistry
Description
Title: Dynamics and mechanisms of CRISPR-Cas9 through the lens of computational methods
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 are instrumental in understanding the dynamics and mechanism of CRISPR-Cas9 and pave the way for a new field of computational studies aimed at deciphering and engineering genome editing systems.
