Current Issue : April - June Volume : 2013 Issue Number : 2 Articles : 6 Articles
Background: Protein-protein recognition is of fundamental importance in the vast majority of biological processes.\r\nHowever, it has already been demonstrated that it is very hard to distinguish true complexes from false complexes\r\nin so-called cross-docking experiments, where binary protein complexes are separated and the isolated proteins are\r\nall docked against each other and scored. Does this result, at least in part, reflect a physical reality? False complexes\r\ncould reflect possible nonspecific or weak associations.\r\nResults: In this paper, we investigate the twilight zone of protein-protein interactions, building on an interesting\r\noutcome of cross-docking experiments: false complexes seem to favor residues from the true interaction site,\r\nsuggesting that randomly chosen partners dock in a non-random fashion on protein surfaces. Here, we carry out\r\narbitrary docking of a non-redundant data set of 198 proteins, with more than 300 randomly chosen \"probe\"\r\nproteins. We investigate the tendency of arbitrary partners to aggregate at localized regions of the protein surfaces,\r\nthe shape and compositional bias of the generated interfaces, and the potential of this property to predict\r\nbiologically relevant binding sites. We show that the non-random localization of arbitrary partners after proteinprotein\r\ndocking is a generic feature of protein structures. The interfaces generated in this way are not systematically\r\nplanar or curved, but tend to be closer than average to the center of the proteins. These results can be used to\r\npredict biological interfaces with an AUC value up to 0.69 alone, and 0.72 when used in combination with\r\nevolutionary information. An appropriate choice of random partners and number of docking models make this\r\nmethod computationally practical. It is also noted that nonspecific interfaces can point to alternate interaction sites\r\nin the case of proteins with multiple interfaces. We illustrate the usefulness of arbitrary docking using PEBP\r\n(Phosphatidylethanolamine binding protein), a kinase inhibitor with multiple partners.\r\nConclusions: An approach using arbitrary docking, and based solely on physical properties, can successfully identify\r\nbiologically pertinent protein interfaces....
New drug discovery is considered broadly in terms of two kinds of investigational activities such as exploration and exploitation. The current study deals with the evaluation of the cyclooxygenase inhibitory activity of flavonoids using in silico docking studies. In this perspective, flavonoids like Peonidin, Robinetin, Isorhamnetin, Biochanin, Herbacetin, Butein, Fisetin, Apigenin, Baicalin were selected. Celecoxib, a known cyclooxygenase inhibitor was used as the standard. In silico docking studies were carried out using AutoDock 4.2, based on the Lamarckian genetic algorithm principle. Three important parameters like binding energy, inhibition constant and intermolecular energy were determined. The results showed that all the selected flavonoids showed binding energy ranging between -8.39 kcal/mol to -6.42 kcal/mol when compared with that of the standard (-8.30 kcal/mol). Intermolecular energy (-10.18 kcal/mol to -8.21 kcal/mol) and inhibition constant (708.47 nM to 19.52 µM) of the ligands also coincide with the binding energy. All the selected flavonoids contributed cyclooxygenase inhibitory activity because of its structural parameters. These molecular docking analyses could lead to the further development of potent cyclooxygenase inhibitors for the treatment of inflammation....
In the present investigation we are reporting docking simulation analysis of one triazole congener which we have reported earlier. The Docking studies were performed by using Autodock software and results are expressed as rmsd score of different conformation of ligand into the assumed binding site of cyclo-oxygenase 2 receptor. The analysis reveals that triazole analogues interact with putative binding site by hydrogen bonding and arene-cation contacts. Based on the present analysis, further structure modification can be carried out to improve the anti-inflammatory potential of reported analogue....
Ligand-based and structure-based drug screening methods were integrated for in\r\nsilico drug development by combining the maximum-volume overlap (MVO) method with a\r\nprotein-compound docking program. The MVO method is used to select reliable docking\r\nposes by calculating volume overlaps between the docking pose in question and the known\r\nligand docking pose, if at least a single protein-ligand complex structure is known. In the\r\npresent study, the compounds in a database were docked onto a target protein that had a\r\nknown protein-ligand complex structure. The new score is the summation of the docking\r\nscore and the MVO score, which is the measure of the volume overlap between the docking\r\nposes of the compound in question and the known ligand. The compounds were sorted\r\naccording to the new score. The in silico screening results were improved by comparing the\r\nMVO score to the original docking score only. The present method was also applied to some\r\ntarget proteins with known ligands, and the results demonstrated that it worked well....
Viscosine was isolated from Dodonaea viscosa, which showed significant\r\nlipoxygenase inhibitory activity (IC50: value 39 �± 0.17). Molecular docking\r\nsimulations were conducted to explore molecular binding mode, and to help\r\nelucidate molecular mechanism behind its significant inhibitory activity.\r\nMolecular interactions of viscosine with catalytic triad (His523, His518, Ile875)\r\ninside active site of lipoxygenase via hydrogen bonding, seems to be the major\r\nfactor involved in its significant lipoxygenase inhibitory activity....
New conjugates of quinoxaline - 2, 3 (1H, 4H) dione containing pioglitazone, glimepiride and thiosemicarbazide moieties were synthesized as mannich base to interpret the effect of quinoxaline on antidiabetic potential of current drugs. Quinoxalin - 2, 3 (1H, 4H) - dione was treated with respective antidiabetic moieties and thiosemicarbazide and the reaction products were purified and characterized by IR, 1H NMR, 13C NMR, Mass Spectral and elemental data. The acute oral toxicity study indicated that no mortality was observed for the synthesized compounds at a given test dose of 500 mg/Kg b.w/ p.o. Compounds were evaluated for antidiabetic activity in male Wistar albino rats. Thiosemicarbazide of quinoxaline mannich base showed significant antidiabetic activity with p value of < 0.001 and comparable with Pioglitazone. Pioglitazone derivatives exhibited better onset of action than parent pioglitazone and also recorded the potent hypoglycemic profile than parent drug. Docking analysis was performed to support the binding affinity of new Ligands on PPAR2 receptor....
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