478 papers
IDPForge is an open-source, transformer-based diffusion model that generates accurate all-atom conformational ensembles for intrinsically disordered proteins and regions without requiring sequence-specific training or experimental reweighting, thereby addressing the limitations of current structure prediction tools in modeling dynamic protein disorder.
This study employs molecular modeling techniques to demonstrate that the RS stereoisomer of prasugrel's active metabolite exhibits preferential, stereoselective binding to the closed P2Y12 receptor conformation, driven by a more energetically favorable disulfide bridge formation with cysteine 175 and distinct interactions with extracellular loops compared to other stereoisomers.
This study employs a machine learning framework to analyze experimental structural databases, revealing that class A GPCR activation follows a hybrid mechanism where ligand binding selects pre-existing active-like conformations while G protein binding induces a stable active state, thereby providing a practical tool for understanding activation dynamics and guiding drug discovery.
By surveying prokaryotes with small genomes, this study identifies a minimal ion channel repertoire dominated by mechanosensitive channels, suggesting that the ability to monitor physical membrane integrity evolved prior to the need for electrical communication.
This study establishes a structure-activity relationship for mRNA lipid nanoparticles, demonstrating that a more ordered internal structure, evidenced by specific small-angle X-ray scattering characteristics, strongly correlates with enhanced in vitro activity, while processes like lyophilization that disrupt this order diminish efficacy.
This study demonstrates that the direction of cell durotaxis is not an intrinsic property but a tunable behavior determined by culture conditions, where conventional 2D plastic substrates induce migration toward stiff regions while preconditioning in soft 3D physiomimetic environments reprograms cells to migrate toward softer, physiologically relevant stiffnesses.
By applying nondimensional nucleus shape parameters derived from a mechanical model to high-frequency 3D imaging of cells migrating through microchannels, this study reveals that cells actively regulate actin tension and nuclear envelope compliance to maintain mechanical homeostasis (mechanostasis) specifically during high-confinement migration.
Using multiscale modeling, this study demonstrates that plant cell wall creep arises from the stochastic sliding of cellulose microfibrils via localized dislocation-like defects, a mechanism that enables sustained wall expansion under turgor pressure while maintaining structural integrity through microfibril bundling rather than reorientation.
Using cryo-electron tomography, this study reveals that RNA polymerases and DNA-binding proteins preferentially localize at plectoneme apices to act as torsional blocks that segregate twin-supercoiling domains, where the resulting load-and-release mechanism driven by topoisomerase I provides a structural basis for transcriptional bursting.
This paper presents a physics-grounded evaluation revealing that state-of-the-art protein structure prediction models, while capturing basic energetic principles, exhibit pervasive biases in atomic interactions and conformational preferences that limit their accuracy and generalizability, thereby highlighting the need for such frameworks to guide the development of next-generation models capable of reliable biomolecular function prediction.
This study demonstrates a novel approach using cryogenic electron tomography (cryoET) to quantitatively determine Rubisco polymerization constants within α-carboxysomes by converting in situ particle positions and volumes into binding curves, thereby establishing cryoET as a powerful tool for analyzing biomolecular interactions in their native environment.
This study reveals that human mitochondrial tryptophanyl-tRNA synthetase requires both ATP and Mg2+ to achieve high-affinity indolmycin binding through a reinforced ground-state metal coordination mechanism that structurally and thermodynamically mimics bacterial enzymes, contrasting sharply with the binding properties of human cytoplasmic TrpRS.
This study demonstrates that the C-terminal domain of the coronavirus envelope protein forms amyloid-like filaments capable of modulating liposome membrane shape, offering a potential mechanism for how the E protein interacts with host cell membranes.
This paper introduces Bilayer Acoustic Force Spectroscopy (BAFS), a high-precision method that utilizes antigen-functionalized lipid bilayers to eliminate non-specific binding and quantify receptor-antigen binding strengths in immune synapses, thereby enabling more accurate screening and mechanistic insights for cancer immunotherapy.
This paper introduces Bio-Spin Probabilistic Inference (BISPIN), a digital statistical framework that leverages enhanced nitrogen-vacancy quantum sensors to quantify previously inaccessible, weak stochastic magnetic fluctuations in living cells, thereby enabling robust cellular phenotyping and a new dimension of bio-spin omics.
This study systematically evaluates various design components of FRET-based vinculin tension sensors to establish a comparative framework for interpreting force measurements and provide practical guidelines for optimizing molecular probe engineering.
Using a laser-trap assay to resolve previous contradictions in tissue-level studies, this research demonstrates that caldesmon acts as a critical molecular regulator in smooth muscle by inhibiting force generation through competitive actomyosin binding and accelerating relaxation, thereby offering new insights into the pathophysiology of disorders like hypertension and asthma.
This study presents the first molecular structures of active Photosystem I-platinum nanoparticle biohybrids to define the interface topology and electron transfer pathways, thereby establishing design principles for optimizing protein-nanomaterial architectures for solar fuel production.
This study demonstrates that Repetitive Extragenic Palindrome (REP) elements in *E. coli* function as context-dependent dual regulators of 3'UTRs by simultaneously acting as partial Rho-dependent transcription terminators and mRNA stabilizers, thereby tuning gene expression and contributing to regulatory diversity across strains without altering coding sequences.
Using cryo-electron tomography, this study reveals that influenza hemagglutinin trimers on native virions form flexible, locally ordered lattices through lateral HA1-mediated interactions, which are essential for coordinating membrane fusion and facilitating efficient viral entry.