Molecular mechanism of CRISPR-Cas9 

micioCRISPR-Cas9 is a revolutionary genome editing tool, which enables to easily manipulate nucleic acids. Our labs uses computational methods to unravel the function and improve biological applications of CRISPR genome-editing machineries. We have described the mechanism of RNA binding and the association with the nucleic acids, delivering also molecular details on the off-target effectsWe revealed an intriguing mechanism of allosteric regulation and  we  recently described the activation process of the HNH domain (figure) and the catalytic state of the system, prone to perform genome editing.


[1] East K. et al. J. Am. Chem. Soc. 2020. [2] Palermo G. J. Chem. Inf. Model. 2019. [3] Ricci C. G. et al. ACS Cent. Sci. 2019. [4] Palermo G. Chem 2019. [5] Palermo G. et al. Q. Rev. Biophys. 2018. [6] Palermo G. et al. J. Am. Chem. Soc. 2017. [7] Palermo G. et al. Proc. Natl. Acad. Sci. USA, 2017. [8] Palermo G. et al. ACS Cent. Sci. 2016.

                                                                Read our latest story in ChemRxiv and our article in Physics Today                                                                                                                                   

Catalytic Metals and Enzymatic Processing of DNA & RNA



As originally revealed by Steitz & Steitz (PNAS 1993), DNA & RNA endonucleases perform phosphodiester bond cleavage using two metal ions. We are interested in using computational methods to understand the metal-aided catalysis in DNA and RNA processing enzymes. Our interest in understanding the role of metal ions and the functional differences in the catalysis of RNA & DNA.


[1] Palermo G. et al. Acc. Chem. Res. 2015. [2] Palermo G. et al. J. Chem. Theory Comput. 2013. [3] Palermo G. et al. Chem. Commun. 2015. 

Non-coding RNA & splicing


RNA is a fundamental molecule that codes for protein and controls gene expression, playing a key regulation role in many cell responses and vital processes, such as human genetic heritance and diseases. We are interested in clarifying the molecular basis of non-coding RNA, which regulates gene expression via a variety of yet unknown mechanisms. We have suggested a mechanism for the splicing reaction in the bacterial groupII intron, and studied the functional dynamics of the human splicesome.


[1] Palermo G. et al. J. Struct. Biol. 2019. [2] Casalino L. et al. Proc. Natl. Acad. Sci. USA 2018. [3] Casalino L. et al.  J. Am. Chem. Soc. 2016. [4] Casalino L. et al. J. Chem. Theory Comput. 2017.

Nucleosome dynamics & chromatin drug development


The constituents of chromatin, chromosomal DNA and histone proteins, are key molecular targets for anticancer drugs. By integrating molecular dynamics with X-ray crystallography and biochemical assays, we have characterized the mechanism of action of promising metal-based anticancer agents at the level of the nucleosome core particle, the fundamental unit of chromatin. 


[1] Adhrikenesan Z. et al. Nat. Commun. 2017. [2] Ma Z. et al. Angew. Chem. Int. Ed. 2016 [3] Palermo G. et al. ChemMedChem 2016