Open Questions on Viral Frameshifting: Exploiting Structural Plasticity of the Frameshifting Element for Therapeutic Intervention Monday, May 18, 2026 Programmed Ribosomal Frameshifting (PRF) is a specialized controlled-slippage genetic mechanism that viruses like SARS-CoV-2 and HIV-1 use to shift the reading frame during translation. This process is used in compact viral genomes to enhance their protein repertoire, maintain a precise balance of viral proteins necessary for successful replication, and enhance survival within a host. Because this mechanism is vital to the viral life cycle and remains consistent across strains, frameshifting has emerged as a promising therapeutic target for new antiviral therapeutic strategies. Read more
19F NMR Probes of Conformational Change in a Bifurcating Electron Transfer Flavoprotein Monday, May 18, 2026 Bifurcating electron transfer flavoproteins (bETFs) accept a pair of modestly reducing electrons and produce a more potent electron carrier based on energy derived from favorable transfer of the other electron. A domain-scale conformational change is believed to gate electron transfer within the bETF, allowing only one electron to use the favorable path. 80° rotation of the so-called head domain carries the electron-transfer FAD (ET-FAD) from near the bifurcating FAD in bETF's closed conformation, to a position > 35 Å away in bETF's open conformation. Read more
Telomeres in Lamin-A Depleted Cells Exhibit Directed Motion and Dynamic Coherence Monday, May 18, 2026 Investigating the dynamics of chromatin loci and the factors that influence them provides valuable insights into the organization and functionality of the genome within the cell nucleus. We control the expression of Lamin-A, an important organizer of chromatin and nuclear structure. By simultaneously tracking hundreds of telomeres in Lamin-A knocked-out (KO) and wild-type (WT) nuclei, we find that telomere motion in Lamin-A depleted cells is both faster and more directed on micrometer scales, comparable to the size of chromosome territories. Read more
Quantifying interleaflet coupling of phase behavior and observing anti-registered phases in asymmetric lipid bilayers Friday, May 15, 2026 Biological membranes are compositionally asymmetric, with distinct lipid mixtures in each leaflet, yet how this asymmetry influences lateral membrane organization remains poorly understood. Here, we use calcium-induced hemifusion to generate asymmetric giant unilamellar vesicles (aGUVs) and investigate how lipid composition modulates interleaflet coupling of liquid-liquid phase separation. Symmetric GUVs composed of cholesterol, the high-melting lipid DPPC, and a low-melting phosphatidylcholine (either 14:1-PC or 16:1-PC) were prepared at compositions exhibiting coexisting liquid-ordered (Lo) and liquid-disordered (Ld) phases. Read more
One Chromatin, Many Structures: From Ensemble Contact Maps to Single-Cell 3D Organization Friday, May 15, 2026 Understanding how chromatin folds in three dimensions remains challenging because most experimental assays capture low-dimensional projections of an underlying, highly heterogeneous polymer. Here we present an ensemble-based interpretive framework built on the previously introduced Self-Returning Excluded Volume (SR-EV) model, a minimal generator of chromatin conformations using a nucleosome-indexed coarse-grained representation based on stochastic return rules and excluded-volume geometry. Despite its simplicity, SR-EV recapitulates key experimental signatures across scales: heterogeneous nanoscale packing domains resembling ChromEMT and ChromSTEM observations, sparse and highly variable single-configuration contact patterns analogous to single-cell chromosome conformation capture (Hi-C), and robust ensemble-level contact enrichment consistent with topologically associating domains (TADs). Read more
General anaesthetic modulation of a pentameric ligand-gated ion channel explored with simulations Friday, May 15, 2026 General anaesthetics are known to modulate pentameric ligand-gated ion channels (pLGICs), including GABAA, glycine, serotonin and glutamate receptors, among others. The bacterial (Gloeobacter) ion channel GLIC captures anaesthetic modulation while providing high-resolution structures in each of its distinct functional conformations, allowing for molecular definition of state-dependent binding and quantification of allosteric mechanisms. This study uses molecular dynamics, metadynamics and free energy simulations to calculate the free energy surfaces of propofol binding to open and closed channels. Read more
Bacterial lipids traverse the hydrophobic groove of TamB Thursday, May 14, 2026 The double-membrane envelope of Gram-negative bacteria protects it against environmental stress and antibiotics. Phospholipids are a core component of the bacterial outer membrane (OM). However, how phospholipids are transported to the OM from the inner membrane (IM) where they are synthesized is poorly understood. We show that the AsmA-like protein TamB transfers lipids through a large hydrophobic groove which directly bridges the inner and outer membranes. Lipid dissociation at the outer membrane is impeded when TamB is bound to its OM partner protein TamA but lipids can spontaneously enter the groove in simulations where the C-terminus of TamB is embedded in the OM. Read more
Ablation, Percolation, and Afterdepolarization Wednesday, May 13, 2026 Ablation is an effective treatment for cardiac arrhythmias, and its primary goal is to remove excitability from cells to break pathological reentrant circuits or focal activities and thereby prevent recurrent arrhythmias. Ablation prevents excitation by destroying cells in targeted regions. However, if ablation does not eliminate sufficient cells, waves of action potentials (APs) may continue to propagate, and ablation may fail to suppress arrhythmias. In this study, we develop a theoretical approach that predicts the minimum number of ablated cells to break reentrant circuits and suppress the initiation and propagation of focal activities. Read more
Iomeprol X-ray contrast media alter conformation and affinity of the ATP binding pocket of actin Wednesday, May 13, 2026 Contrast materials are widely used in various X-ray/CT and MRI diagnostic procedures. When administered in high volumes, contrast agents can strain kidney function and lead to acute renal failure. Contrast materials may damage the plasma membrane and penetrate into tissue cells. Some iodine-based contrast agents have been reported to distort the shape of red blood cells, implying a rearrangement of the actin cytoskeletal network. As actin plays a crucial role in numerous cellular processes, the effects of iodine-based contrast media on actin require clarification. Read more
Protein Function-Conditioned Language Models for Variant Effect Prediction and Controllable Design Wednesday, May 13, 2026 Protein function-conditioned generative modeling can unify two core goals in protein engineering: predicting the effects of sequence variants and designing new sequences that satisfy functional constraints. We present a framework that conditions protein language modeling on molecular function semantics encoded from the Gene Ontology (GO) as a text-attributed directed acyclic graph. By embedding GO text and ontology topology, our function embedding captures relationships among functions and supports cross-function transfer. Read more