The Comprehensive VS Platform with AI Engine (CVSP-AIE) for drug discovery from compound libraries integrates three AI models: KarmaDock, a fast docking model that directly updates atomic coordinates; CarsiDock, an accurate docking model that predicts protein-ligand distances and reconstructs binding poses; and RTMScore, an accurate scoring model that learns residue-atom distance distributions for affinity prediction.
The producers occupy distinct ER-proteostasis states, and DUL mounts a broader, but not uniformly stronger, canonical UPR response to reductive ER stress.
N. Orlova, N. A. Potapova, R. R. Shaifutdinov et al.· International Journal of Mol...· 0 citations
Widespread disturbances in amino acid metabolism were identified via untargeted metabolomics in HCC patients with metastasis, closely governing inflammation-related metabolic remodeling and oxidative stress responses.
Jing Wu, Jin Wang, Zhen Yu et al.· Frontiers in Immunology· 0 citations
It is indicated that chlorogenic acid influences testicular oxidative status and ferroptosis-related gene responses under acrylamide exposure, supporting its potential relevance as a dietary component for acrylamide-associated reproductive oxidative stress.
Hasan Hüseyin Keçeli, A. Yakan, Hüseyin Özkan· Ankara Üniversitesi Veterine...· 0 citations
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Dysphagia-adapted fluidized meat products alter the protein matrix structure and may impair digestibility. This work evaluated the digestive and nutritional properties of carboxymethyl cellulose (CMC)-modified myofibrillar protein (MP) thickened fluids across three matrices: liquid solution (MP), semisolid state (MP/CMC), and solid gel (MPgel). In vitro digestion indicated all MP matrices exhibited lower digestibility under elderly digestive conditions than adult systems, especially during gastric stage. CMC promoted protein hydrolysis by enhancing the accessibility of MP to pepsin. Digestive kinetics implied that initial and maximal gastric digestion rates of MP/CMC for adults were 13.07- and 3.65-fold higher than those of liquid MP, while dense cross-linked networks reduced digestion extent and rates in MP gel. In vivo, CMC thickening slowed gastrointestinal transit of semisolid MP, sustaining abundant gastric peptides and maintaining high steady-state serum total amino acids in mice. This work provided fundamental insights into the digestive and nutritional characteristics of CMC-induced meat protein-based fluids.
Jiale Chai, Jingjie Wang, Yue Wang et al.· Journal of Agricultural and...· 0 citations
Higher order protein structural predictions suggested that the putative epistatic interactions among E180V, G184V, and G252V, D253G may be associated with S protein folding and structural stability.
M. Jogi, Sristy Shikha, Pushpendra Singh et al.· Frontiers in Immunology· 0 citations
Fluorescence-based immunoassays are widely used for sensitive and specific biomarker detection; however, further improvements in sensitivity remain desirable for detecting low-abundance analytes without increasing assay complexity. In this work, we present a proof-of-concept demonstration of guided electrokinetic assembly of functionalized latex beads as a post-assay signal enhancement strategy using alternating-current electro-osmosis (ACEO). Carboxyl-modified 1 μm polystyrene beads conjugated with Alexa Fluor 647-labeled anti-IgG were localized within lithographically defined windows on carbon interdigitated electrode arrays, producing localized fluorescence enhancement through physical bead localization without enzymatic amplification or additional labeling chemistries. Compatibility of the approach with fluorescence-based immunoassays was demonstrated through adaptation of a TNF-α ELISA workflow. Electro-osmotic localization of functionalized bead conjugates was achieved within 120 s, producing an approximately 12-fold increase in corrected total fluorescence relative to the corrected signal of the pre-electro-osmosis condition while demonstrating negligible enrichment of unbound fluorescent protein. Application of the platform to a TNF-α sandwich immunoassay yielded an approximately 5.5-fold enhancement in fluorescence signal, and robust bead localization was maintained across anti-IgG concentrations ranging from 1 to 4 μg/mL. These findings demonstrate that guided electrokinetic bead localization provides an effective signal enhancement strategy for fluorescence-based immunoassays and represents a promising approach for improving the detection of low-abundance analytes.
T. Zhou, Alfonso Shin, L. Kulinsky· Italian National Conference...· 0 citations
In vivo evidence is provided for choroid plexus dysfunction in a maternally inherited disorder with convergent evidence supporting a mitochondrial aetiology, associated with reduced CSF production and impaired blood–CSF barrier transport, substantially altering biomarker profiles in the absence of cortical atrophy or blood–brain barrier disruption.
P. Selnes, J. Jarholm, Antón Vila-Sanjurjo et al.· Fluids and Barriers of the C...· 0 citations
Breast cancer remains one of the leading causes of cancer-related mortality among women worldwide, necessitating the development of safer and more targeted therapeutic strategies. This study computationally extends our previous experimental investigation of a peptide derived from
Lacticaseibacillus casei
by evaluating its interactions with two clinically relevant breast cancer targets, estrogen receptor alpha (ERα; PDB ID: 3ERT) and human epidermal growth factor receptor 2 (HER2; PDB ID: 1N8Z).
The peptide structure was predicted using PEP-FOLD and its stereochemical quality was assessed using a Ramachandran plot. Molecular docking was performed against ERα and HER2, followed by molecular dynamics simulations to evaluate structural stability. Binding free energy, binding affinity, dissociation constant, principal component analysis (PCA), free energy landscape (FEL), molecular mechanics (MM)/Poisson–Boltzmann surface area (PBSA) calculations, and
in silico
ADMET and toxicity predictions were performed to comprehensively characterise peptide–protein interactions.
The predicted peptide model exhibited 84.8% of residues located in the most favoured regions, while 15.2% were located in additionally allowed regions of the Ramachandran plot, indicating satisfactory stereochemical quality. Molecular docking demonstrated favourable interactions with both ERα and HER2, with HER2 showing a marginally more favourable docking score. Molecular dynamics simulations indicated stable peptide–protein complexes throughout the simulation period, as supported by root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), solvent-accessible surface area (SASA), and hydrogen-bond analyses. MM/PBSA calculations predicted stronger binding for the HER2 (1N8Z) complex (ΔG = −28.83 kJ/mol) than for the ERα (3ERT) complex (ΔG = −11.65 kJ/mol), highlighting the complementary nature of docking and dynamic free-energy estimation, which produced different receptor rankings. PCA and FEL analyses further demonstrated stable conformational sampling for both complexes. ADMET predictions suggested favourable peptide-like physicochemical properties while identifying pharmacokinetic and toxicity parameters that require further experimental validation.
This computational study suggests that the
L. casei
-derived peptide exhibits favourable predicted interactions with ERα and HER2 and forms structurally stable peptide–protein complexes under simulated physiological conditions. These findings provide a computational framework for prioritising this probiotic-derived peptide for subsequent experimental validation and further investigation as a potential peptide-based therapeutic candidate for breast cancer.
G. R. Shree Kumari, M. Vaithilingam· Frontiers in Bioinformatics· 0 citations
This work investigates how protein folding landscapes are altered inside condensates, using the protein α-helix as a model folded domain and develops a chemically specific, residue-resolution model for quantification of α-helical folding and applies it to characterize diverse helices within condensates of varying physicochemical properties.
Nathaniel Hess, Jerelle A. Joseph· Journal of the American Chem...· 0 citations
The quaternary ammonium strategy represents an effective approach to developing water-soluble PD-1/PD-L1 inhibitors with dual immunomodulatory and antiangiogenic functions.
Jianwei Xu, Pan Yang, Xixiang Yang et al.· Journal of Medicinal Chemist...· 0 citations
These findings establish NABi as a promising therapeutic candidate for SOD1G93A-associated familial ALS, demonstrating its capacity to selectively target pathological protein conformations while preserving normal cellular function.
Min-Kyung Nam, Yeram Oh, Yemi Choi et al.· ACS Chemical Neuroscience· 0 citations
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.