Computational Biology and Chemistry, Journal Year: 2023, Volume and Issue: 108, P. 107981 - 107981
Published: Nov. 7, 2023
Language: Английский
Computers in Biology and Medicine, Journal Year: 2024, Volume and Issue: 179, P. 108898 - 108898
Published: July 23, 2024
Language: Английский
Citations
7
Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)
Published: Aug. 5, 2024
Globoid cell leukodystrophy is a severe rare disorder characterized by white matter degradation, resulting in progressive loss of physical and mental abilities has extremely limited therapeutic interventions. Therefore, this study aimed to delve into the associated intricate network differentially expressed genes (p < 0.05, |Fc|> 1) identify potential druggable targets possible interventions using small molecules. The disease-associated neuronal protein circuit was constructed analyzed, identifying 53 nodes (minimum edge cutoff 1), among which five (FOS, FOSB, GDNF, GFRA1, JUN) were discerned as core nodes. Although our research enumerates molecules target various proposed disease network, we particularly underscore T-5224 inhibit c-Jun activity JUN identified one pivotal elements within circuit. evaluation binding energy (− 11.0 kcal/mol) from docking revealed that compound exhibit notable affinity towards Jun/CRE complex. Moreover, structural integrity complex affirmed through comprehensive molecular dynamics simulations, indicating stable hydrophilic interaction between complex, thereby enhancing compactness reducing solvent accessibility. This further substantiated free analysis, revealing substantial thermodynamics state 448.00 ± 41.73 kJ/mol). Given investigation confined computational framework, additionally propose hypothetical framework ascertain feasibility inhibiting with against leukodystrophy, employing combination vitro vivo methodologies prospective avenue study.
Language: Английский
Citations
4
Chemistry & Biodiversity, Journal Year: 2025, Volume and Issue: unknown
Published: March 11, 2025
Transient receptor potential vanilloid 3 (TRPV3) is a thermosensitive calcium-permeable ion channel and has function in sensory perception, epidermal barrier function, inflammation keratinocyte proliferation. TRPV3 dysfunction linked with chronic pain, atopic dermatitis neurodegenerative disorders. This study compared the binding efficacy molecular dynamics of cannabidiol- eugenol-TRPV3 complex(s), elucidating their ligand-protein dynamics. Computational methods, including density functional theory, docking simulations, assessed electronic properties, affinities interaction stability, respectively. Cannabidiol showed higher affinity (-7.73 ± 0.73 kcal/mol) than eugenol (-6.0 0.05 kcal/mol), driven by denser hydrophilic hydrophobic contacts. Molecular revealed cannabidiol-TRPV3 complex steady atomic deviation protein compactness. Furthermore, cannabidiol-induced diverse conformational states, while exhibited greater flexibility. These findings highlight cannabidiol's stable, dynamic TRPV3, suggesting its to exert TRPV3-mediated biological effects. In contrast, may serve transient modulation. offers insights into ligand-ion interactions, guiding drug development for TRPV3-related conditions.
Language: Английский
Citations
0
Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16
Published: March 18, 2025
Disulfiram (DSF) is an anti-alcoholic drug that has been reported to inhibit the epithelial-to-mesenchymal transition and crosslinking during fibrosis, pyroptosis, inflammatory NF-κB Nrf-2 signaling pathways. However, there insufficient evidence support mechanisms of DSF in preventing renal fibrosis (RF). Therefore, current study aimed elucidate DSF-modulated targets pathways fibrosis. The common proteins between RF were screened for protein-protein interaction, pathway enrichment, cluster, gene ontology analysis. Molecular docking was executed core genes using AutoDock Vina through POAP pipeline. dynamics (MD) simulation (100 ns) performed infer protein-ligand stability, conformational changes analyzed by free energy landscape (FEL). A total 78 found be RF, which NFKB, PIK3CA/R1, MTOR, PTGS2, MMP9 genes. PI3K-Akt followed JAK-STAT, TNF, Ras, ErbB, p53, phospholipase D, mTOR, IL-17, NF-κB, AMPK, VEGF, MAPK modulated RF. showed a direct binding affinity with active site residues genes, except all other complexes, including standard, stable 100 ns MD minimal root mean squared deviation residual fluctuations higher compactness broad changes. protects against this paves way experimental investigation repurpose treating
Language: Английский
Citations
0
Peptide Science, Journal Year: 2025, Volume and Issue: 117(3)
Published: May 1, 2025
ABSTRACT Breast cancer remains a leading cause of mortality among women aged 45–55, driven by factors such as hormonal imbalances, iodine deficiency, and aging. Significant side effects collateral damage to healthy tissues limit the effectiveness current treatments, surgery, chemotherapy, radiation therapy. Tandyukisin, marine‐derived compound, shows potential novel therapeutic agent targeting drug‐resistant EGFR HER2 mutations. This study investigates Tandyukisin against breast through network pharmacology, molecular docking, dynamics simulations, focusing on its interactions with ERBB2 associated signaling pathways. Potential cancer‐specific targets for were identified SwissTargetPrediction GeneCards databases, overlaps analyzed using Venny 2.1. Functional enrichment protein–protein interaction analyses conducted STRING Cytoscape version 3.10.3. Molecular docking was performed AutoDock Vina assess binding affinity ERBB2, while simulations evaluated stability conformational Tandyukisin‐ERBB2 complexes. 27 cancer‐relevant proteins, prominently ERBB2. analysis revealed role in apoptotic regulation critical pathways like PI3K‐Akt MAPK. In addition, demonstrated strong stable showed complex atomic deviation residual fluctuation, confirming enhanced stability. Additionally, pathway Tandyukisin's disruption resistance VEGF signaling, emphasizing multifactorial anti‐tumor effects. exhibits promising efficacy selectively modulating key pathways, minimizing off‐target Its specificity position it candidate advanced therapy, addressing drug improving outcomes. Further experimental validation is required substantiate these findings.
Language: Английский
Citations
0
Frontiers in Aging Neuroscience, Journal Year: 2025, Volume and Issue: 16
Published: Jan. 13, 2025
Traumatic brain injury (TBI) can generally be divided into focal damage and diffuse damage, neonate Hypoxia-Ischemia Brain Damage (nHIBD) is one of the causes damage. Patients with nHIBD are at an increased risk developing Alzheimer's disease (AD). However, shared pathogenesis patients affected both neurological disorders has not been fully elucidated. We here aim to identify molecular signatures between AD. used integrated analysis cortex gene expression data, targeting differential genes related mechanisms neurodegeneration cognitive impairment following traumatic injury. The profiles (GSE203206) that Neonate (GSE23317) were obtained from Gene Expression Omnibus (GEO) database. After identifying common differentially expressed (DEGs) by limma package analysis, five kinds analyses performed on them, namely Ontology (GO) pathway enrichment protein-protein interaction network, DEG-transcription factor interactions DEG-microRNA interactions, protein-drug protein-disease association gene-inflammation protein-inflammation analysis. In total, 12 DEGs identified including HSPB1, VIM, MVD, TUBB4A, AACS, ANXA6, DIRAS2, RPH3A, CEND1, KALM, THOP1, AREL1. also 11 hub proteins, three central regulatory transcription factors, microRNAs encoded DEGs. Protein-drug showed CYC1 UQCRFS1 associated different drugs. Gene-disease shows Mammary Neoplasms, Neoplasm Metastasis, Schizophrenia, Ischemia diseases most relevant proteins we identified. Gene-inflammation AREL1 inflammatory response, while AKT1 MAPK14 response. This study provides new insights AD nHIBD. These pathways could potentially design therapeutic interventions, reducing likelihood development in survivors neonatal Hypoxic-Ischemia
Language: Английский
Citations
0
3 Biotech, Journal Year: 2025, Volume and Issue: 15(5)
Published: April 3, 2025
Language: Английский
Citations
0
RSC Advances, Journal Year: 2024, Volume and Issue: 14(6), P. 4188 - 4200
Published: Jan. 1, 2024
Network pharmacology, molecular docking, and dynamics simulations identify quercetin 3-O-β- d -glucopyranosyl-(1→2)-rhamnopyranoside as a promising inhibitor of HRAS VEGFA proteins, suggesting potential use Drymaria cordata natural source for treating cervical cancer.
Language: Английский
Citations
2
Schizophrenia Research, Journal Year: 2024, Volume and Issue: 271, P. 38 - 46
Published: July 14, 2024
Language: Английский
Citations
2
Molecular Simulation, Journal Year: 2024, Volume and Issue: 50(15), P. 1170 - 1182
Published: Aug. 13, 2024
Outbreaks of human Nipah virus (NiV) cases have recently been reported in several countries. With a mortality rate around 80% and no known therapy, there is an urgent need to test existing antivirals repurposed for it. Due its central role replication, the RNA-dependent RNA polymerase (RdRp) NiV-L protein potential target such antiviral therapies. In this study, Favipiravir, Remdesivir, Ribavirin, their metabolites, including monophosphate (MP), diphosphate (DP), triphosphate (TP), were virtually screened against RdRp. Using molecular dynamics (MD) simulations, lead hits from docking study examined conformational changes. Additional analyses, MM-PBSA, residual decomposition energy, principal component analysis, performed on MD trajectory. Remdesivir-TP, Favipiravir-TP, Ribavirin-TP exhibited lowest binding energies –7.8, −7.4, −6.9 kcal/mol, respectively, displayed affinity pocket 1, forming interactions with active site residues Asp726 Asn727. During 100 ns simulation, Remdesivir-TP demonstrated more stable mode compared Favipiravir-TP Ribavirin-TP. The relative −94.709 kJ/mol, −68.882 −46.98 kJ/mol Ribavirin-TP, respectively. This research anticipates be candidate drug NiV infection.
Language: Английский
Citations
2