Biomolecular force fields have continuously evolved to improve their accuracy and broaden their applications in biological and therapeutic discoveries. The rapid adaptation of advanced computational technology, in particular the recent deep learning revolution, has led to an unprecedented ability to model and simulate biomolecules, as well as new opportunities in force field parametrization. Here,

In this issue of Structure, Gong et al.1 provide structural insights into the diversity of bacterial ubiquitin-like proteins and characterize their Ca2+-dependent oligomerization into dimers and filaments. Their findings suggest a potential mechanism by which fluctuations in metal-ion concentrations could modulate bacterial stress-response pathways.

Visualizing subcellular distributions of proteins and assessing their colocalization patterns are central to understanding the organization and interactions of molecular assemblies. In this issue of Structure, Kiuchi et al.1 introduce protein cluster coloring to map complex association patterns among eight endogenous proteins at the periphery of the clathrin-coated structure, revealing their multilayered

Mass photometry (MP) is a label-free approach that measures the mass of single molecules in solution. Here, we discuss the principles of MP, example uses of the technique, and how it can be a valuable tool for structural biologists in streamlining cryoelectron microscopy (cryo-EM) pipelines.

Insulin binding to the insulin receptor (IR) induces large conformational changes leading to receptor activation. Although there exists a considerable number of IR structures in different conformational and insulin-saturation states, they cannot provide dynamic information or the resolved order of events leading to receptor activation. In this study, we employed molecular dynamics (MD) simulations

The interaction network of Sla2, a vital endocytic mid-coat adaptor protein, undergoes constant rearrangement. Sla2 serves as a scaffold linking the membrane to the actin cytoskeleton, with its role modulated by the clathrin light chain (CLC), which inhibits Sla2’s function under certain conditions. We show that Sla2 has two independent binding sites for CLC: one previously described in homologs of

In this Voices article, we introduce eight impressive scientists at different career stages who spoke at the recent “8th Ringberg Workshop on Structural Biology (with FELs)” organized by Ilme Schlichting from the Max Planck Institute for Medical Research, Heidelberg. We asked the authors to tell us more about themselves and their exciting research.

The Ad5-nCoV vaccine (Convidecia) against COVID-19 showed promising clinical results. However, the molecular mechanisms underlying its high immunogenicity and potential adverse reactions have remained elusive. In this issue of Structure, Dong et al.1 employed cryo-electron tomography as a powerful technique to show that abundant prefusion spike protein formation is induced by Ad5-nCoV vaccines.

In this issue of Structure, Horatscheck et al.1 report the isolation and characterization of two improved small molecule drugs for the selective inhibition of clathrin-mediated endocytosis.

Membrane proteins function within lipid membranes but require mimetics for structural studies. In this issue of Structure, Hoffmann et al.1 show how different mimetics bias the conformational spectrum of the MsbA transporter. This study highlights the need for improved membrane mimetics and sustained efforts to link conformations to function.

(Structure 33, 740–752; April 3, 2025)

In this issue of Structure, Banerjee et al.1 use single-molecule FRET to explore how various detergents and cholesterol influence the conformational dynamics of the extracellular domain of the metabotropic glutamate receptor 2 (mGluR2). They show that the local membrane environment modulates the receptor’s active-inactive state equilibrium and identifies specific cholesterol-binding sites, offering

In a recent issue of Cell Chemical Biology, De Paula et al.1 report an extensive methyl-TROSY solution NMR study of the CRISPR-Cas9 holoenzyme. Studying millisecond-to-second protein dynamics using individual domain constructs of Cas9 coupled to structural interrogations of the full-length enzyme, the authors describe the Cas9 “surveillance state,” a molecular mechanism driving the discrimination between

ATP-binding cassette (ABC) transporters are critical for cellular processes, facilitating the transport of various substrates across membranes by harnessing ATP hydrolysis. These transporters are divided into importers and exporters, with importers playing key roles in nutrient uptake and bacterial virulence. Despite their therapeutic potential as drug targets, the regulatory mechanisms governing ABC