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Fo domain of ATP synthase functions as a rotary molecular motor, coupling proton translocation with the rotation of the c-ring rotor. This process involves proton uptake at the entry half channel, rotor rotation, and proton release to the exit half channel. While the overall coupling mechanism is established, the design principle for efficient rotation remains unclear. Here, we employed hybrid molecular simulations—combining coarse-grained modeling and Monte Carlo methods—to investigate the roles of side chain flexibility at proton-binding residues and the angular mismatch between the proton uptake process and the proton release process.

Stochastic modeling of transcription is a classic yet long-standing problem in theoretical biophysics. The lack of unified results and a computationally efficient approach for a general, fine-grained transcription model has confined relevant research to some over-simplified special cases like the Telegraph model. This article establishes a general, unified and computationally efficient framework for studying stochastic transcription kinetics. We consider a chemical reaction model of transcription and construct the time-dependent solution to the corresponding chemical master equation.

The degree of unsaturation in lipids, which refers to the number of double bonds in their acyl chains, influences properties such as fluidity and lipid packing. However, it is not well understood how the unsaturation affects the ability of peptides to sense membrane curvature. In our study, we compared membranes with varying levels of unsaturation: mono-unsaturated POPC; bis-unsaturated DOPC; and poly-unsaturated PAPC. We investigated how these membranes interact with peptides of varying hydrophobicity.

MicroRNAs (miRNAs) are ubiquitous short RNAs regulating gene expression in many organisms, including humans. How the secondary structure (SS) of a mature miRNA affects its regulatory function remains an open question. Here we investigate this question through computational SS predictions of miRNA point mutants. We explore the mutational neighborhoods of miRNAs with association to human diseases, including cancer. We focus on possible SS changes independent of target-site complementarity, by leaving the seed region unchanged.

(Biophysical Journal 124, 2383–2390; August 5, 2025)

The amino acid proline is accumulated in a variety of plant species in response to environmental stresses such as high salinity and extreme temperatures. Whilst the colligative role of proline as an osmoprotectant is well known, its influence on molecular interactions within the cell has received less attention. Here, we investigate the effects of proline on interaction free energies in aqueous environments, and we find that the presence of proline significantly enhances the repulsive force between charged surfaces relative to pure water.

DNA elements such as genes and their regulatory regions must become accessible for protein binding when transcription is activated, which requires reorganization of the nucleosomes that fold the DNA into chromatin fibers. MNase-seq has been instrumental in uncovering the interplay between gene activity and chromatin organization by mapping the average nucleosome occupancy in populations of cells. However, better mechanistic understanding can be obtained from assays that can map nucleosomes along long strands of DNA at single-molecule resolution and without averaging.

Antibody Fab fragments are widely used protein binders that assist in structural studies of G protein-coupled receptor (GPCR) signaling complexes. Expanding the repertoire of such binders to target distinct components of the signaling complex offers opportunities to probe conformational regulation and dynamics. Here, we report the biochemical and cryo-EM characterization of two Fab fragments, Fab79 and Fab13, raised against the rhodopsin-Gαiβγ complex. Fab79 binds to the flexible α-helical domain (AHD) of the Gαi subunit and prevents complex dissociation in the presence of the non-hydrolyzable GTP analog, GTPγS, likely by hindering AHD closure, a step necessary for complex dissociation.

Spatiotemporal dynamics of calcium regulation in subcellular regions is critical for precise local control of cell signaling. Recent studies have shown that, in addition to biochemical control of localized calcium signaling through buffers and channels, the geometry of the small spaces in which calcium signaling occurs also matters. Geometric organization becomes particularly important when considering the role of organelles such as the mitochondria and endoplasmic reticulum in regulating calcium signaling.

Gene expression is a stochastic process that leads to variability in mRNA and protein abundances even within an isogenic population of cells grown in the same environment. This variation, often called gene-expression noise, has typically been attributed to transcriptional and translational processes while ignoring the contributions of protein decay variability across cells. Here we estimate the single-cell protein decay rates of two degron GFPs in Saccharomyces cerevisiae using time-lapse microscopy.

Within the disordered tangles of Tau is a proline-rich region (PRR) which is selectively targeted by the SH3 domain of BIN1, a known genetic factor for Alzheimer’s disease, and may hold the key to understanding the disorder and treatment strategies. Hyperphosphorylation of Tau is known to disrupt complex formation, providing researchers with an excellent preventative or remediative targets. This work compiles an extensive (>60 μs) collection of all-atomistic molecular dynamics (MD) simulations of the Tau(210-240) fragment, representing the majority of the P2 subdomain of the PRR, benchmarking various forcefields, phosphorylations, and modifications against experimental NMR chemical shifts and spin-spin coupling for comparison.