Principles of target DNA cleavage and the role of Mg2+ in the catalysis of CRISPR–Cas9

Ł Nierzwicki, KW East, JM Binz, RV Hsu, M Ahsan… - Nature …, 2022 - nature.com
At the core of the CRISPR–Cas9 genome-editing technology, the endonuclease Cas9
introduces site-specific breaks in DNA. However, precise mechanistic information to …

Twisting and swiveling domain motions in Cas9 to recognize target DNA duplexes, make double-strand breaks, and release cleaved duplexes

J Wang, PR Arantes, M Ahsan, S Sinha… - Frontiers in molecular …, 2023 - frontiersin.org
The CRISPR-associated protein 9 (Cas9) has been engineered as a precise gene editing
tool to make double-strand breaks. CRISPR-associated protein 9 binds the folded guide …

Pairing structural reconstruction with catalytic competence to evaluate the mechanisms of key enzymes in the folate‐mediated one‐carbon pathway

LN Zhao, P Kaldis - The FEBS Journal, 2023 - Wiley Online Library
Mammalian metabolism comprises a series of interlinking pathways that include two major
cycles: the folate and methionine cycles. The folate‐mediated metabolic cycle uses several …

The electronic structure of genome editors from the first principles

Ł Nierzwicki, M Ahsan, G Palermo - Electronic Structure, 2023 - iopscience.iop.org
Ab-initio molecular dynamics enables following the dynamics of biological systems from the
first principles, describing the electronic structure and offering the opportunity to" watch" the …

Leveraging QM/MM and Molecular Dynamics Simulations to Decipher the Reaction Mechanism of the Cas9 HNH Domain to Investigate Off-Target Effects

Y Maghsoud, VM Jayasinghe-Arachchige… - Journal of Chemical …, 2023 - ACS Publications
The clustered regularly interspaced short palindromic repeats (CRISPR) technology is an
RNA-guided targeted genome-editing tool using Cas family proteins. Two magnesium …

Molecular dynamics-derived descriptor informs the impact of mutation on the catalytic turnover number in lactonase across substrates

Y Jiang, B Yan, Y Chen, RJ Juarez… - The Journal of Physical …, 2022 - ACS Publications
Molecular dynamics simulations have been extensively employed to reveal the roles of
protein dynamics in mediating enzyme catalysis. However, simulation-derived predictive …

An interaction network in Bacillus subtilis coproporphyrinogen oxidase is essential for the oxidation of protoporphyrinogen IX

B Wang, L Sun, X Wen, Z Xi - Proteins: Structure, Function, and …, 2023 - Wiley Online Library
Coproporphyrinogen oxidase (CPO) plays important role in the biosynthesis of heme by
catalyzing the coproporphyrinogen III to coproporphyrin III. However, in earlier research, it …

The catalytic mechanism of the mitochondrial methylenetetrahydrofolate dehydrogenase/cyclohydrolase (MTHFD2)

LN Zhao, P Kaldis - PLoS Computational Biology, 2022 - journals.plos.org
Methylenetetrahydrofolate dehydrogenase/cyclohydrolase (MTHFD2) is a new drug target
that is expressed in cancer cells but not in normal adult cells, which provides an Achilles …

Deciphering the Thermodynamic Landscape of CRISPR/Cas9: Insights into Enhancing Gene Editing Precision and Efficiency

A Kumar, P Daripa, K Rasool… - The Journal of …, 2024 - ACS Publications
The thermodynamic landscape of the CRISPR/Cas9 system plays a crucial role in
understanding and optimizing the performance of this revolutionary genome-editing …

Molecular basis of the reaction mechanism of the methyltransferase HENMT1

P Kaldis, LN Zhao - Plos one, 2024 - journals.plos.org
PIWI-interacting RNAs (piRNAs) are important for ensuring the integrity of the germline. 3'-
terminal 2'-O-methylation is essential for piRNA maturation and to protect them from …