Our lab uses computer simulations to unravel the function and improve biological applications of emerging genome editing systems that are transforming life sciences. Using state-of-the-art computational methods, we described conformational activation, catalysis, allostery and selectivity of CRISPR-Cas9 and other large macromolecular machines acting on genes.
We apply and develop hybrid computational approaches based on molecular dynamics and free energy simulations, quantum mechanical methods and cryo-electron microscopy (cryo-EM) processing techniques. We complement these methods with graph theory and emerging network models, to describe the intricate communication mechanisms in biological systems. Our findings are fully integrated with data obtained from experimental techniques, including cryo-EM, single-molecule spectroscopy and NMR.
Our interest in in pushing the frontiers of computational biophysics to access large spatio-temporal scales and tackle dynamics and mechnisms of emerging biological systems obtained through cryo-EM.
Selected Publications
2024: A. Saha, M. Ahsan,* P. R. Arantes,* M. Schmitz, C. Chanez, M. Jinek and G. Palermo.† An Alpha-helical Lid Guides the Target DNA toward Catalysis in CRISPR-Cas12a. 2024 Nat. Commun. accepted, available at BioRxiv: doi: 10.1101/2022.09.05.5066
2023: S. Sinha, A. M. Molina Vargas, P. R. Arantes,* A. Patel,* M R. O’Connell.† and G. Palermo.† Unveiling the RNA-mediated allosteric activation discloses functional hotspots in CRISPR-Cas13a. Nucleic Acids Res. 2023, gkad1127.
2022: Ł. Nierzwicki, K. W. East, J. Binz, R. V. Hsu, M. Ahsan, P. R. Arantes, E. Skeens, M. Pacesa, M. Jinek, G. P. Lisi† and G. Palermo.† Principles of Target DNA Cleavage and Role of Mg2+ in the Catalysis of CRISPR-Cas9. Nature Catal. 2022, 5, 912-922. PDF
2021: Ł. Nierzwicki, K. W. East, U. N. Morzan, P. R. Arantes, V. S. Batista, G. P. Lisi† and G. Palermo.† Enhanced Specificity Mutations Perturb Allosteric Signaling in CRISPR-Cas9. eLife 2021, 10: e73601.
2020: L. Casalino, Ł. Nierzwicki, M. Jinek and G. Palermo.† Catalytic Mechanism of Non-Target DNA Cleavage in CRISPR-Cas9 Revealed by Ab-Initio Molecular Dynamics. ACS Catalysis, 2020, 22, 13596-13605.
2019: C. G. Ricci, J. S. Chen, Y. Miao, M. Jinek, J. A. Doudna, J. A. McCammon and G. Palermo.† Deciphering Off-target Effects in CRISPR-Cas9 through Accelerated Molecular Dynamics. ACS Cent. Sci. 2019, 5, 651-662.
Palermo Lab 