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257 papers
This study enhances the understanding of the E. coli-genome nature and suggests the existence of specific and experimentally testable novel prions in this organism, and moves a step forward towards the identification of new prion proteins in bacteria.
Milk proteins deliver nutritional, functional, and bioactive properties that alternative protein sources cannot adequately replicate, yet conventional livestock-based production faces compounding constraints of scalability, resource intensity, and sustainability. Precision fermentation offers a structurally distinct solution, but existing reviews have addressed neither a systematic cross-species framework for target selection nor a treatment of post-translational modifications (PTMs) gap-bridging, leaving critical gaps in rational pipeline design. This review integrates four analyses: a cross-species comparison of sequence, structural, and PTMs characteristics across human, bovine, goat, and camel milk proteins to inform target prioritization; a consolidation of advances in host engineering, fermentation scale-up, and downstream purification; a structural-functional comparison of precision-fermented and native milk proteins encompassing phosphorylation, disulfide bond pairing, and glycosylation fidelity, alongside strategies for bridging identified PTMs gaps; and an evaluation of AI-driven optimization strategies for heterologous milk protein expression. Cross-species analysis favors human-derived sequences for infant nutrition and immunity, while ruminant proteins excel in expression compatibility and scalability. α-Lactalbumin and β-lactoglobulin are the most tractable targets given minimal PTM dependency; caseins and lactoferrin require intracellular phosphorylation and glycosylation unavailable in microbial hosts. AI accelerates process optimization but cannot yet co-optimize yield, folding fidelity, and PTM accuracy, a key frontier for next-generation engineering. Scale-up robustness, glycoengineering consistency, and regulatory definition remain underexplored.
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.
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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.
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.
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