molecular docking

Oxidative stress is a central pathomechanism in chronic kidney disease (CKD), yet the nephroprotective potential of Fernandoa adenophylla (Bignoniaceae), a medicinally important tree of South and Southeast Asia, remains mechanistically uncharacterised. This study employed an integrated network pharmacology and molecular docking strategy to systematically elucidate the multi-target mechanism of F. adenophylla against oxidative stress-mediated renal injury. Thirteen phytochemical constituents were retrieved from curated databases and subjected to ADME screening via SwissADME; eight compounds including lapachol, α-lapachone, adenophyllone, peshwaraquinone, ursolic acid, and oleanolic acid met Lipinski’s Rule-of-Five criteria and were retained. Protein targets for these compounds were predicted via SwissTargetPrediction and intersected with 287 oxidative stress nephroprotection disease targets retrieved from GeneCards, OMIM, DisGeNET, and TTD, yielding 53 shared candidate targets. A tripartite Compound–Target–Disease network constructed in Cytoscape identified AKT1, TP53, NFE2L2 (NRF2), KEAP1, CASP3, and MAPK1 as principal hub targets. STRING-based protein–protein interaction analysis and CytoHubba MCC ranking corroborated these hubs, while GO and KEGG enrichment mapped the target set to the PI3K/AKT, apoptosis, NF-κB, and HIF-1α signalling pathways. Molecular docking with AutoDock Vina revealed that adenophyllone exhibited the highest binding affinity for KEAP1 (−8.9 kcal/mol) and lapachol for AKT1 (−8.2 kcal/mol). These interactions were further validated by 100 ns GROMACS molecular dynamics simulations demonstrating stable RMSD profiles, sustained hydrogen-bond occupancy, and favourable MM-PBSA binding free energies. Collectively, these results indicate that F. adenophylla likely exerts nephroprotection through coordinated modulation of the KEAP1/NRF2 antioxidant axis, the AKT1/TP53/CASP3 survival–apoptosis axis, and the MAPK1/TNF inflammatory–oxidative crosstalk axis, providing a rational computational foundation for in-vitro and in-vivo experimental validation.

1,3,4 – thiadiazole derivatives derived from various reaction sequences with slight modifications in the side chain with primary amine group at 5th position in the thiadiazole ring. The docking studies were done by using scroodinger software version against the enzyme protein kinase. The structures of all the compounds were drawn using chemdraw software version 8.0. All the thiadiazole derivatives showed satisfactory ligand binding energy between -2.70 to -5.60 k.cal /mole. Compounds A3, A21,M34&M36 showed better glide score with -5.4, -4.9, -4.7 and-4.00 respectively.

Streptococcus gordonii are one among the early colonisers of tooth surfaces of humans and are present in coronal plaque, gingival crevices and buccal and pharyngeal mucosal surfaces. One of the main virulence factor that is involved in S. gordonii adhesion and coaggregation is ScaA protein. Inactivation of scaA genes resulted in both impaired growth of cells and inhibition of Mn2+ intake. Thus the inhibitors of ScaA protein can act as an effective drug against S. gordonii especially in the prevention and treatment of infective endocarditis and dental caries. The three dimensional structure of ScaA protein is predicted by homology modelling. It is the method to determine 3D structure of protein with the help of 3D structure of homologous proteins. Softwares used are Modeller 9.11 and Easy modeller 2.0 GUI. A total of 500 ligands in 2D format were derived from myricetin with the help of software ACD chemsketch. Rapid virtual screenings of these compounds were performed in the docking tool iGEMDOCK v2.0. Based on the binding energy a total of three ligands were selected for the further study. Three ligands thus generated possessed very good docking energy. Thus three ligands with good inhibitory properties were generated among which 5-[3,4-dihydroxy-6-(pyridin-2-yl)-8aH-chromen-2-yl]benzene-1,2,3-triol, a novel compound is found to be very excellent drug candidate based on the molecular docking studies and its ADME properties.