478 papers
This study elucidates the structural mechanism and species-specific selectivity of Necrocide 1 in activating human TRPM4 to induce necrotic cell death via sodium overload, providing a foundation for developing TRPM4-targeted cancer therapeutics.
This study demonstrates that lipid nanoparticles with less compact, low-order siRNA packing mediate more efficient gene silencing than highly ordered counterparts, providing a new framework for optimizing LNP formulations by tuning composition and N/P ratios to favor this specific packing mode.
This paper presents thermodynamically consistent bond graph models of the Na+/K+-ATPase to demonstrate that the pump operates at approximately 75% efficiency under physiological conditions, while identifying a critical ATP hydrolysis energy threshold below which its function is severely compromised.
This paper introduces a rigorous zero-field singlet-triplet basis framework that clarifies the low-field effect in radical pairs as a sequential process where weak magnetic fields unlock access to singlet-accessible triplet manifolds, thereby providing a transparent physical mechanism and a general method for estimating the effect's upper bound.
This study demonstrates that PI(4,5)P2 is a critical endogenous modulator of GABAAR and glycine receptor function, where its high-affinity binding to the K311 site on the α1 subunit is essential for maintaining normal channel activation kinetics and preventing sensitivity to acute lipid depletion.
The authors present a Gouy-Chapman-based continuum electrostatics model, accompanied by a Python implementation, to predict how salt concentration and membrane composition shift the effective pKa of ionizable lipids in lipid nanoparticles, thereby aiding in the optimization of RNA delivery formulations.
This study elucidates the molecular architecture and ligand-gating mechanism of the human GluD1 receptor using cryo-electron microscopy and single-channel recordings, revealing how GABA or D-serine binding triggers cation influx and providing a structural foundation for understanding neurological diseases and developing targeted therapies.
This study demonstrates that fusing intrinsically disordered protein domains to receptor ligands enables precise control over receptor endocytosis by modulating intermolecular interactions to either drive membrane condensation for internalization or prevent it to retain receptors on the cell surface.
The authors introduce 2BPA-HB, a novel sequence-resolved coarse-grained model that successfully captures the dual nature of FG-nucleoporins by simulating their transitions between disordered condensates and ordered amyloid fibrils within a single computational framework.
This study reveals that protein language models like ESM-2 function as evolutionary grammar compressors that capture macroscopic sequence statistics rather than microscopic 3D geometries, leading to a fundamental conflation of distinct thermodynamic phases and topological anomalies due to their reliance on statistical correlations over explicit physical folding principles.
This study identifies specific critical amino acid residues within the disordered N-terminal domain of the NADPH-dependent assimilatory sulfite reductase flavoprotein that are necessary and sufficient to mediate its stable octameric assembly, providing new insights for engineering homomeric protein complexes.
This study employs molecular dynamics simulations to demonstrate that the polyQ tract length and sequence context within the disordered ELF3-PrD domain modulate temperature-sensitive helix formation and the exposure of aromatic residues, thereby governing the heat-induced condensation of the Evening Complex that regulates plant growth.
This study demonstrates that short-term exposure to silver ions disrupts the locomotion of Drosophila melanogaster larvae in a concentration- and time-dependent manner by reducing crawling speed and distance while trapping them in a stop phase due to the inhibition of rhythmic peristaltic contractions.
This study utilizes multi-scale serial femtosecond crystallography to reveal that while insulin detemir and insulin aspart share increased conformational heterogeneity at ambient temperatures compared to cryogenic conditions, they exhibit distinct, analog-specific disorder patterns characterized by detemir's pseudo-translational signatures and aspart's pronounced merohedral twinning, all while maintaining stable backbone stereochemistry.
This study introduces a Metabolic Spin-Glass model optimized by quantum annealing to recast cancer metabolism as a frustrated many-body system, revealing that malignant phenotypes represent distinct thermodynamic ground states where the Warburg effect emerges as a phase transition and enabling the identification of prognostically distinct patient subtypes through a novel energy-based order parameter.
This study uses molecular dynamics simulations to demonstrate that specific LQT2-associated missense mutations in hERG channels impair trafficking by allosterically disrupting the structural integrity of the selectivity filter, while identifying a second-site variant that can correct these defects.
This paper reports the development and characterization of fluorescent membrane scaffold proteins (MSPs) that retain the structural integrity and purification efficiency of conventional MSPs while enabling versatile applications through C-terminal fluorescent tags like HaloTag.
This study introduces a label-free, depth-adaptive 4D holotomography framework to longitudinally quantify single lipid droplet dynamics in living hepatic organoids, revealing that oleic acid and linoleic acid drive lipid accumulation through distinct mechanisms of droplet enlargement versus proliferation, respectively, while palmitic acid rapidly compromises organoid integrity.
This study demonstrates the repeatable execution on real quantum hardware (IBM Pittsburgh) of a minimal four-qubit surrogate model for fast local-topology hyperthermal sarcomeric oscillations, achieving strong agreement between experimental results and exact simulations for key biologically interpretable observables.
This study utilizes extensive molecular dynamics simulations to characterize the distinct RISE and OPEN intercalation modes of doxorubicin, SYBR Gold, and YOYO-1 on DNA, revealing how these binding mechanisms differentially alter conformational dynamics, mechanical properties, and binding affinities through stacking-driven interactions.