Current Issue : October - December Volume : 2012 Issue Number : 4 Articles : 5 Articles
HIV-1 (human immunodeficiency virus type-1) is the pathogenic retrovirus and causative agent of AIDS. The integrase enzyme offers an attractive target for anti-AIDS drug design because of its necessary for viral life cycle and lack of IN homologous enzymes in the human host. Structural features of L-chicoric acid are important for potency against HIV-1 integrase. So, in the present study, 2-D QSAR and interaction studies of some chicoric acid analogs was carried out by VLife MDS & Schrodinger molecular modeling interface. The developed QSAR models showed r2= 0.8503, pred_r2 = 0.8201 with MLR analysis. Docking study also revealed important interactions of these ligands with the active binding site of integrase enzyme. These studies are more significant guide to trace the features that really matter especially with respect to the design of novel compounds....
Constitutive STAT signaling provides growth promoting signals in many forms of malignancy. We performed molecular\r\nmodeling and molecular dynamics studies of the interaction between the regulatory Src homology 2 (SH2) domains of\r\nSTAT3 and 6 with phosphorylated peptides of the herpesviral oncoprotein Tip, which facilitates Src kinase mediated STATactivation\r\nand T cell proliferation. The studies give insight into the ligand binding specificity of the STAT SH2 domains and\r\nprovide the first model for the differential activation of STAT3 or STAT6 by two distinct regions of the viral Tip protein. The\r\nbiological relevance of the modeled interactions was then confirmed by activation studies using corresponding\r\nrecombinant oncoproteins, and finally by respective recombinant viruses. The functional data give experimental validation\r\nof the molecular dynamics study, and provide evidence for the involvement of STAT6 in the herpesvirus induced T cell\r\nproliferation....
Peroxidases (POD) and polyphenol oxidase (PPO) are enzymes that are well\r\nknown to be involved in the enzymatic browning reaction of fruits and vegetables with\r\ndifferent catalytic mechanisms. Both enzymes have some common substrates, but each also\r\nhas its specific substrates. In our computational study, the amino acid sequence of grape\r\nperoxidase (ABX) was used for the construction of models employing homology modeling\r\nmethod based on the X-ray structure of cytosolic ascorbate peroxidase from pea (PDB\r\nID:1APX), whereas the model of grape polyphenol oxidase was obtained directly from the\r\navailable X-ray structure (PDB ID:2P3X). Molecular docking of common substrates of\r\nthese two enzymes was subsequently studied. It was found that epicatechin and catechin\r\nexhibited high affinity with both enzymes, even though POD and PPO have different\r\nbinding pockets regarding the size and the key amino acids involved in binding. Predicted\r\nbinding modes of substrates with both enzymes were also compared. The calculated docking interaction energy of trihydroxybenzoic acid related compounds shows high\r\naffinity, suggesting specificity and potential use as common inhibitor to grape ascorbate\r\nperoxidase and polyphenol oxidase...
Chiral separations of five -adrenergic antagonists (propranolol, esmolol, atenolol,\r\nmetoprolol, and bisoprolol) were studied by capillary electrophoresis using six cyclodextrins\r\n(CDs) as the chiral selectors. Carboxymethylated--cyclodextrin (CM--CD) exhibited a\r\nhigher enantioselectivity power compared to the other tested CDs. The influences of the\r\nconcentration of CM--CD, buffer pH, buffer concentration, temperature, and applied\r\nvoltage were investigated. The good chiral separation of five -adrenergic antagonists was\r\nachieved using 50 mM Tris buffer at pH 4.0 containing 8 mM CM--CD with an applied\r\nvoltage of 24 kV at 20 Ã?°C. In order to understand possible chiral recognition mechanisms\r\nof these racemates with CM--CD, host-guest binding procedures of CM--CD and these\r\nracemates were studied using the molecular docking software Autodock. The binding free\r\nenergy was calculated using the Autodock semi-empirical binding free energy function.\r\nThe results showed that the phenyl or naphthyl ring inserted in the hydrophobic cavity\r\nof CM--CD and the side chain was found to point out of the cyclodextrin rim. Hydrogen\r\nbonding between CM--CD and these racemates played an important role in the process of\r\nenantionseparation and a model of the hydrogen bonding interaction positions was\r\nconstructed. The difference in hydrogen bonding formed with the ââ?¬â??OH next to the chiral center of the analytes may help to increase chiral discrimination and gave rise to a bigger\r\nseparation factor. In addition, the longer side chain in the hydrophobic phenyl ring of the\r\nenantiomer was not beneficial for enantioseparation and the chiral selectivity factor was\r\nfound to correspond to the difference in binding free energy....
Abstract\r\nToll-like receptors (TLRs) are pattern recognition receptors that recognize pathogens based on distinct molecular signatures.\r\nThe human (h)TLR1, 2, 6 and 10 belong to the hTLR1 subfamilies, which are localized in the extracellular regions and activated\r\nin response to diverse ligand molecules. Due to the unavailability of the hTLR10 crystal structure, the understanding of its\r\nhomo and heterodimerization with hTLR2 and hTLR1 and the ligand responsible for its activation is limited. To improve our\r\nunderstanding of the TLR10 receptor-ligand interaction, we used homology modeling to construct a three dimensional (3D)\r\nstructure of hTLR10 and refined the model through molecular dynamics (MD) simulations. We utilized the optimized structures\r\nfor the molecular docking in order to identify the potential site of interactions between the homo and heterodimer (hTLR10/2\r\nand hTLR10/1). The docked complexes were then used for interaction with ligands (Pam3CSK4 and PamCysPamSK4) using\r\nMOE-Dock and ASEDock. Our docking studies have shown the binding orientations of hTLR10 heterodimer to be similar with\r\nother TLR2 family members. However, the binding orientation of hTLR10 homodimer is different from the heterodimer due to\r\nthe presence of negative charged surfaces at the LRR11-14, thereby providing a specific cavity for ligand binding. Moreover,\r\nthe multiple protein-ligand docking approach revealed that Pam3CSK4 might be the ligand for the hTLR10/2 complex and\r\nPamCysPamSK4, a di-acylated peptide, might activate hTLR10/1 hetero and hTLR10 homodimer. Therefore, the current\r\nmodeled complexes can be a useful tool for further experimental studies on TLR biology....
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