protein folding

Sublethal heat stress-induced HSF4 upregulation via GRSF1 in an m6A-dependent manner in hepatocellular carcinoma.

BACKGROUND Sublethal heat stress exacerbates hepatocellular carcinoma (HCC) by promoting recurrence and metastasis. This study aimed to investigate the molecular mechanisms by which sublethal heat stress enhances HCC progression to improve therapeutic strategies and patient outcomes in HCC management. METHODS Cell-ba...

Proteomics based analysis of the therapeutic mechanism of Yishen Gushu Formula against postmenopausal osteoporosis.

It is suggested that YSGSF may improve PMOP by coordinating nitrogen metabolism, circadian regulation, extracellular-matrix remodeling, and lipid metabolism through a three-target regulatory network.

A Protein-Imprinted Polymer Encapsulates Aggregation-Induced Emission Luminogens for Enhanced Near-Infrared-II Imaging and Photothermal Eradication of Bacterial Biofilms.

This study overcomes the intrinsic trade-off between radiative and non-radiative decay pathways in aggregation-induced emission luminogens (AIEgens) for phototheranostic applications and enables effective imaging-guided eradication of MRSA in back and joint abscess models.

Agmatine as the initiating substrate for aspartate semialdehyde-dependent bacterial spermidine biosynthesis.

The substrate specificity of the B. fragilis and C. leptum enzymes is redefined, a mechanistic model for agmatine-dependent catalysis in alternative spermidine biosynthesis is established, and a testable framework for predicting substrate specificity is provided across this family of bacterial polyamine biosynthetic en...

Transcriptional reprogramming with endogenous cis- and trans-elements for efficient food protein expression from safe substrates in Komagataella phaffii.

Sustainable economy and social development require a paradigm shift in the modes of production of edible proteins. Komagataella phaffii is a preferred host for food protein expression. However, its methanol-dependent production mode and host improvement with exogenous bioelements pose challenges for the manufacturing a...

Combinatorial deep mutational scanning uncovers protein superbinders and molecular determinants of epistasis.

Traditional deep mutational scanning (DMS) encodes every single amino-acid substitution from a wild-type sequence. We hypothesize that combinatorial DMS (CDMS) libraries, incorporating all mutations in all combinations, can enable the discovery of high-affinity protein (super)binders by capturing epistatic, non-linear...

Examining Protein Residue-Level Stability Using Theory and Experiment

Experimental grounding for the theoretical principles that govern protein sequence energetics are provided, inspiring a complementary Sequence Probability INverse (SPIN) framework, which characterizes optimality through a Boltzmann-weighted selection probability within an ensemble of sequences.

Editorial: Advancing pediatric critical care: sepsis, immune dysregulation, and precision therapies

Pediatric critical care stands at a pivotal intersection of developmental immunology, organ system physiology, and rapidly evolving therapeutic innovation. Sepsis remains the leading cause of morbidity and mortality in pediatric intensive care units (PICUs) worldwide, accounting for over 20% of global childhood deaths...

Integrated AI-Driven Multi-Objective Optimization of Sulfamoylbenzamide-Based HBV Capsid Assembly Modulators: Discovery of 11B-6 with Superior Potency and Drug-like Properties

Current capsid assembly modulators (CAMs) require improvements in antiviral potency and drug-like properties. Herein, we report a multi-objective optimization workflow for the NVR 3-778 by integrating structure-based fragment growing with systematic medicinal chemistry optimization, activity prediction, and multitask...

Unraveling protein folding and structural dynamics

Domain classification of archaeal proteomes reveals conserved fold repertoire

Archaea represent one of the three domains of cellular life and yet account for fewer than 1% of experimentally determined protein structures, leaving the extent of their structural novelty unknown. Here we present a systematic domain-level classification of 124,075 proteins from 65 archaeal classes spanning 21 phyla a...

Deep learning for protein folding