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331 papers
The first numerical study of continuous-time flow and diffusion models is presented, in which time-dependent potentials and states are represented as tensor networks, and a coherent amplitude encoding is prepared that can be post-processed by quantum algorithms offering a quadratic advantage over Monte Carlo sampling.
Nucleoside natural products exhibit diverse chemical architectures and potent biological activities, yet the biosynthetic strategies that generate their structural diversity remain incompletely understood. Here, we elucidate the early stage biosynthetic pathway of the cytidyl–cyclitol natural product K-563 and its derivatives. The cyclitol component is generated by the myo-inositol-1-phosphate synthase (MIPS) family enzyme KesM and is subsequently coupled to the cytidine moiety by KesL using cytidine 5′-triphosphate (CTP), followed by further modifications catalyzed by the phosphatase KesI and the unique dehydrogenase complex KesJ/KesK. The X-ray crystal structure and mutagenesis analyses reveal that KesL adopts the canonical fold of S-adenosyl-l-methionine (SAM) synthetases, which catalyze the adenosylation of l-methionine with adenosine 5′-triphosphate (ATP) in primary metabolism, while the KesL active site is extensively remodeled to accept the cyclitol phosphate with CTP as an atypical substrate pair, thereby generating the cytidyl–cyclitol core structure. This work not only expands the chemical logic of nucleoside biosynthesis but also demonstrates how the SAM synthetase-like protein scaffold is repurposed to catalyze an unusual nucleoside transfer reaction for specialized secondary metabolite assembly.
A multimodal early warning system integrating PROs, laboratory trajectories, and large language model-extracted clinical text features to enable real-time, automated complication surveillance substantially outperforms single-modality approaches for detecting postoperative complications after esophagectomy.
Quantitative proteomic profiling of acquired chemoresistant oesophageal adenocarcinoma cell models identifies broad adaptive changes with both heterogeneous and recurrent components, and suggests a platinum-class component supported by overlap between oxaliplatin- and carboplatin-resistant models.
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Postoperative CRP trajectory patterns are significantly associated with complication severity after esophagectomy, and the High-Persistent trajectory identifies a high-risk subgroup, and the D3/D1 ratio enables early risk stratification by POD 3.
The natural product compounds CNP0456830 and CNP0467494 exhibited the lowest binding free energies for both EGFR and PIK3CA, identifying them as the most promising dual-target inhibitors.
The Extra Trees Classifier consistently achieved the highest average accuracy and F1-score in both Gram type classification and species-level identification, demonstrating superior generalization across datasets.
PandaDock’s empirical scoring function ranks 8th of 25 methods evaluated, ahead of every AutoDock Vina and Vinardo configuration tested, while the GNN scores below Vina, consistent with the within-target ceiling identified on SAIR.
circDesign is presented, an algorithm that explicitly incorporates IRES structural deviation into circRNA sequence design while jointly optimizing codon adaptation and thermodynamic stability and establishes IRES structural preservation as a mechanistic design principle for circRNA engineering and position circDesign as a rational framework for therapeutic circRNA development.
This study illustrates how subtle residue-localized conformational bias can affect the overall protein conformational dynamics influencing protein-protein interactions that are important for cellular functions and related to diseases.
It is suggested that bacterial START domains participate in a remarkably broad range of biological processes-including small-molecule binding, metabolic regulation, enzymatic catalysis, and stress adaptation-rather than traditional lipid transport.
DmaxVgR gene silencing disrupted follicular architecture and reduced vitellogenin uptake by the oocytes, resulting in increased vitellogenin levels in the hemolymph suggest a feedback mechanism regulating YPP production.
A new machine-learning framework aims to improve the success rate of computational protein design while moving away from results that reproduce sequences found in nature.
Scientists are using AlphaFold to strengthen a photosynthesis enzyme for resilient, heat-tolerant crops.
Explore how AlphaFold has accelerated science and fueled a global wave of biological discovery.
AlphaFold has revealed the structure of a key protein behind heart disease