Exploration of phytoconstituents of Medhya Rasayana herbs to identify potential inhibitors for cerebroside sulfotransferase through high-throughput screening DOI Creative Commons
Nivedita Singh, Ajay Singh

Frontiers in Molecular Biosciences, Journal Year: 2024, Volume and Issue: 11

Published: Oct. 9, 2024

(CST) is a key enzyme in sulfatide biosynthesis and regulation of the myelin sheath nervous system. To counter accumulation with deficiency aryl sulfatase A, CST considered target protein substrate reduction therapy metachromatic leukodystrophy. In this study, 461 phytoconstituents from four herbs Medhya Rasayana were screened using multi-pronged virtual screening methods including molecular docking, dynamics (MD) simulation, reverse pharmacophore analysis. The initial top 15 hits was based on binding affinity compounds toward substrate-binding site lowest free energy score cutoff ≤ -7.5 kcal/mol, number conformations largest cluster more than 75. absorption, distribution, metabolism, excretion (ADME) toxicity-based pharmacokinetic analysis delivered hits: 18alpha-glycyrrhetinic acid, lupeol, alpha carotene, beta-carotene, high blood-brain barrier permeability negligible toxicity. Furthermore, 100-ns simulation protein-ligand complexes trajectory structural deviation, compactness, intramolecular interactions, principal component analysis, landscape, dynamic cross-correlation showed potential positioning pocket. Thus, an in-depth interactions pre- post-molecular along mapping, suggests that acid most potent specific inhibitor, while beta-carotene could be second compound for inhibition as it also exhibited overall stability throughout simulation. Therefore, computational drug approach applied study may contribute to development oral drugs therapeutic option

Language: Английский

MD–Ligand–Receptor: A High-Performance Computing Tool for Characterizing Ligand–Receptor Binding Interactions in Molecular Dynamics Trajectories DOI Open Access

Michele Pieroni,

Francesco Madeddu, Jessica Di Martino

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(14), P. 11671 - 11671

Published: July 19, 2023

Molecular dynamics simulation is a widely employed computational technique for studying the dynamic behavior of molecular systems over time. By simulating macromolecular biological consisting drug, receptor and solvated environment with thousands water molecules, MD allows realistic ligand-receptor binding interactions (lrbi) to be studied. In this study, we present MD-ligand-receptor (MDLR), state-of-the-art software designed explore intricate between ligands receptors time using trajectories. Unlike traditional static analysis tools, MDLR goes beyond simply taking snapshot (lrbi), uncovering long-lasting predicting time-dependent inhibitory activity specific drugs. With MDLR, researchers can gain insights into complex systems. Our pipeline optimized high-performance computing, capable efficiently processing vast trajectories on multicore Linux servers or even multinode HPC clusters. latter case, user analyze large in very short To facilitate exploration visualization lrbi, provide an intuitive Python notebook (Jupyter), which users examine interpret results through various graphical representations.

Language: Английский

Citations

25
Synthetic strategies and medicinal chemistry perspectives of dual acting carbonic anhydrase modulators with monoamine oxidase and cholinesterase inhibitors DOI

Sandeep Bindra,

Ehab M. Mostafa, Mohamed A. Abdelgawad

et al.

RSC Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Dual acting carbonic anhydrase modulators with monoamine oxidase and cholinesterase inhibitors.

Language: Английский

Citations

1
How the strength of proteins interactions affects the phase behavior of protein complexes DOI

Qingbo Jiao,

Haoxin Ye, Nan Lv

et al.

Food Hydrocolloids, Journal Year: 2023, Volume and Issue: 149, P. 109654 - 109654

Published: Dec. 13, 2023

Language: Английский

Citations

18
ALDELE: All-Purpose Deep Learning Toolkits for Predicting the Biocatalytic Activities of Enzymes DOI Creative Commons
Xiangwen Wang,

Derek J. Quinn,

Thomas S. Moody

et al.

Journal of Chemical Information and Modeling, Journal Year: 2024, Volume and Issue: 64(8), P. 3123 - 3139

Published: April 4, 2024

Rapidly predicting enzyme properties for catalyzing specific substrates is essential identifying potential enzymes industrial transformations. The demand sustainable production of valuable industry chemicals utilizing biological resources raised a pressing need to speed up biocatalyst screening using machine learning techniques. In this research, we developed an all-purpose deep-learning-based multiple-toolkit (ALDELE) workflow catalysts. ALDELE incorporates both structural and sequence representations proteins, alongside ligands by subgraphs overall physicochemical properties. Comprehensive evaluation demonstrated that can predict the catalytic activities enzymes, particularly, it identifies residue-based hotspots guide engineering generates substrate heat maps explore scope given biocatalyst. Moreover, our models notably match empirical data, reinforcing practicality reliability approach through alignment with confirmed mutation sites. offers facile comprehensive solution integrating different toolkits tailored purposes at affordable computational cost therefore would be discovery new functional their exploitation industry.

Language: Английский

Citations

6
Drug repurposing: a nexus of innovation, science, and potential DOI Creative Commons
Maria Cristina De Rosa, Rituraj Purohit, Alfonso T. García‐Sosa

et al.

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Oct. 19, 2023

The urgency of finding therapeutic solutions for emerging and existing health challenges has never been more pronounced. In the pursuit this goal, value a strategy that makes use resources is being recognized: drug repurposing or repositioning compounds new indications. Such approaches are employed against cancer, rheumatoid arthritis, multiple sclerosis, HIV/AIDS, many other diseases. This Collection, aptly titled "Drug Repurposing", includes research perspectives from scientists at forefront innovative field.

Language: Английский

Citations

13
Molecular engineering of BODIPY-bridged fluorescent probes for lysosome imaging – a computational study DOI

Prince Joby,

R. Ramasamy, Rajadurai Vijay Solomon

et al.

Physical Chemistry Chemical Physics, Journal Year: 2024, Volume and Issue: 26(35), P. 22912 - 22930

Published: Jan. 1, 2024

Tailoring optical properties of BODIPY fused 2-(benzo[ d ]thiazol-2-yl) derivatives to enable near-infrared emission for bioimaging applications through DFT, TDDFT, molecular docking and dynamics calculations.

Language: Английский

Citations

4
Design, synthesis, and antidiabetic evaluation of thiazolidinedione derivatives as potent PPAR-γ Agonists: Insights from molecular docking, MD simulations and invitro studies DOI

Mahendra Gowdru Srinivasa,

Karthik G. Pujar, P. Prabitha

et al.

Journal of Molecular Structure, Journal Year: 2025, Volume and Issue: unknown, P. 141324 - 141324

Published: Jan. 1, 2025

Language: Английский

Citations

0
Deciphering Potent Protein Tyrosine Phosphatase‐1B Inhibitors Through In silico Molecular Docking, MMGBSA, and Molecular Dynamics DOI
Vishnu Malakar, Dhanabal Palanisamy,

Bryan Gowramma

et al.

ChemistrySelect, Journal Year: 2025, Volume and Issue: 10(4)

Published: Jan. 1, 2025

Abstract Alzheimer's disease (AD) stands as the most prevalent progressive neurodegenerative disorder, marked by cognitive impairment, memory loss, and deficits. In present study, targeted protein tyrosine phosphatase 1B (PTP1B), a crucial enzyme involved in various signaling pathways, is associated with AD pathogenesis. Our study employs virtual screening of compounds from an extensive database. Based on docking score, molecular dynamics simulation has been performed for top three compounds, donepezil ertiprotafib comparative molecules. As result, molecules CNP0377119, CNP0390654, CNP0377195, donepezil, were identified favorable scores. Further analyses, including PRIME MMGB‐SA ADMET properties, focused standard amino acids like Asp193 Glu276. 100 ns trajectory, exhibited stability through effective binding properties ligands. These interactions included conformations hydrogen bond formations Asn193, Glu276, Lys197, Glu200, Tyr46. The π‐π stacking also observed Phe196 Phe280. allosteric inhibitor PTP1B directly attaches to WPD loop when cysteine‐phosphate intermediate its open conformation hindering closure loop, thereby inhibiting activity.

Language: Английский

Citations

0
Targeting Cxcr4 and Trpv1 with Α-Conopeptide G1 Derived from Conus Geographus for Glioblastoma: An Integrative In-Silico and Network Pharmacology Approach DOI

Sandhanam Kuppusamy,

Sumithra Mohan

Published: Jan. 1, 2025

Language: Английский

Citations

0
Metabolic profiling and antidiabetic potential of Oedogonium angustistomum, Ulothrix variabilis, and Mougeotia pulchella and their peptides targeting α-amylase and α-glucosidase: In vitro and in silico approaches DOI
Sruthy Elsa Shibu,

Edathiruthi Kottukkal Chandran Baiju,

Singamoorthy Amalraj

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 140877 - 140877

Published: Feb. 1, 2025

Language: Английский

Citations

0