ABSTRACT
Molecular docking is a computational method employed to estimate the binding between a small ligand (the drug candidate) and a protein receptor that has become a standard part of workflow in drug discovery. Generally, when the binding site is known and a molecule is similar to known ligands, the most popular docking methods are rather accurate in the prediction of the geometry. Unfortunately, when the binding site is unknown, the blind docking analysis requires large computational resources and the results are often not accurate. Here we present Yada, a new tool for molecular docking that is capable to distribute efficiently calculations onto general purposes computer grid and that combines biological and structural information of the receptor. Yada is available for Windows and Linux and it is free to download at www.yada.unisa.it .
Subject(s)
Molecular Docking Simulation/methods , Algorithms , Binding Sites , Drug Discovery/methods , Glutathione Transferase/chemistry , Ligands , Protein Binding , Protein ConformationABSTRACT
The effects of different doses of Salmonella typhimurium porins were investigated on human laryngeal epithelial (HEp-2) cells by fluorescence and transmission electron microscopy. The changes observed in microfilament organization suggested an involvement of cytoskeleton in the cell response. Furthermore, morphologic phenomena characterized by ultrastructural membrane modifications also involved the nuclear membrane.
Subject(s)
Porins/pharmacology , Salmonella typhimurium , Cells, Cultured , Epithelium/drug effects , Epithelium/microbiology , Epithelium/ultrastructure , Humans , Microscopy, Electron , Microscopy, FluorescenceABSTRACT
We have investigated the effect of therapeutic doses of diazepam (7 micrograms/mouse) on the association of actin with the macrophage cytoskeleton using cytochemical and morphological methods. Results obtained indicated that diazepam was able to modulate the content of actin in macrophages; such an effect proved to be time-dependent. After fixation and staining for indirect immunofluorescence with actin antibody, peritoneal macrophages from mice treated for short time with diazepam, showed a fluorescent intensity increase compared to control mice. The fluorescent intensity augmented reaching peak value within 14 days of treatment. Afterwards, this value dropped below control value for mice that underwent longer treatments. In the in vitro experiments concentrations of 10(-5) M, diazepam inhibited a well cell spread and a lower amount of actin after 15 min of incubation was also revealed. These results suggest that administration of diazepam in vivo plays a role in both the nonspecific and specific immune response, producing in the macrophages a reorganization process of microfilaments.