Graph theory approaches for molecular dynamics simulations.

Graph theory, a branch of mathematics that focuses on the study of graphs (networks of nodes and edges), provides a robust framework for analysing the structural and functional properties of biomolecules. By leveraging molecular dynamics (MD) simulations, atoms or groups of atoms can be represented as nodes, while their dynamic interactions are depicted as edges. This network-based approach facilitates the characterization of properties such as connectivity, centrality, and modularity, which are essential for understanding the behaviour of molecular systems.

Dimerization of the deaminase domain and locking interactions with Cas9 boost base editing efficiency in ABE8e.

CRISPR-based DNA adenine base editors (ABEs) hold remarkable promises to address human genetic diseases caused by point mutations. ABEs were developed by combining CRISPR-Cas9 with a transfer RNA (tRNA) adenosine deaminase enzyme and through directed evolution, conferring the ability to deaminate DNA. However, the molecular mechanisms driving the efficient DNA deamination in the evolved ABEs remain unresolved.

Unveiling Cas8 Dynamics and Regulation within a transposon-encoded Cascade-TniQ Complex.

The Cascade-TniQ complex unveiled a new paradigm in biology, demonstrating that CRISPR-associated proteins can direct DNA transposition. Despite the tremendous potential of "knocking in" genes at desired sites, the mechanisms underlying DNA binding and transposition remain elusive. In this system, a conformational change of the Cas8 protein is essential for DNA binding, yet how it occurs is unclear.

Emerging Methods and Applications to Decrypt Allostery in Proteins and Nucleic Acids.

Many large protein-nucleic acid complexes exhibit allosteric regulation. In these systems, the propagation of the allosteric signaling is strongly coupled to conformational dynamics and catalytic function, challenging state-of-the-art analytical methods. Here, we review established and innovative approaches used to elucidate allosteric mechanisms in these complexes.