This Perspective proposes practical guidance to the application of AlphaFold2 for structure prediction of different classes of proteins including rigid globular proteins, intrinsically disordered proteins and alternative conformational states. The use of evaluation metrics to predict reliability of the resulting models and their integration with experimental data are also discussed.

The non-enzymatic nature of protein glycation makes it a complicated modification to study. This review focuses on the chemistry of glycation, highlighting new opportunities for developing tools that enable the study of its biological consequences.

The inaugural CRISPR-based drug Casgevy has been approved by several medical agencies, with other CRISPR-based therapies currently in clinical trials. Although there are technological hurdles to overcome, chemical biology has a vital role in developing recent breakthroughs in base editing, prime editing and epigenetic editing into future treatments.

Versatile methods for rapid, reversible and repetitive control of protein localization are lacking. A novel optically controlled dimerization system enables precise control of subcellular protein localization while retaining compatibility with multicolor fluorescence microscopy.

Using a combination of antibody- and LC–MS/MS-based methods, Zhang et al. reveal lysine l-lactylation as the key lactylation isomer in cellular histones, responding dynamically to glycolysis and positively correlating with lactyl-CoA levels, providing insights into the Warburg effect.

Protein misfolding can spread from one molecule to another in infectious prion diseases. The propagation of protein misfolding has been directly observed in single protein molecules. These results showed that pathogenic mutants of the protein superoxide dismutase-1 (SOD1), which causes familial amyotrophic lateral sclerosis, imprint their misfolding onto native wild-type molecules.

González-Delgado et al. developed retron-based editors termed multitrons, which can modify multiple sites on a single genome simultaneously. This technology is compatible with recombineering in prokaryotes and CRISPR editing in eukaryotes with applications in molecular recording, genome minimization and metabolic engineering.

Time-resolved synthesis of target proteins via proximity-triggered protein trans-splicing has now been shown to enable the activation of a diverse set of proteins upon the addition or removal of control elements. This temporal precision allows for monitoring distinct phases in cellular signaling and unveiling the molecular connections of oncofusion kinases, including DNAJ–PKAc.

By engineering a tiny OgeuIscB–ωRNA system and tethering DNA-binding protein Sso7d, the authors developed robust miniature base editors SIminiBEs, which achieved robust C-to-T and A-to-G base transitions with a broad targeting range.

The ICP1 (International Center for Diarrheal Disease Research, Bangladesh cholera phage 1) clustered regularly interspaced short palindromic repeats (CRISPR)–Cas system, which lacks the helical bundle domain in Cas8f, uses Cas1 to mediate the interference stage by connecting Cas2/3 to the DNA-bound CRISPR-associated complex for antiviral defense (Cascade).

The inaugural CRISPR-based drug Casgevy has been approved by several medical agencies, with other CRISPR-based therapies currently in clinical trials. Although there are technological hurdles to overcome, chemical biology has a vital role in developing recent breakthroughs in base editing, prime editing and epigenetic editing into future treatments.