Abstract: Geometry optimizations of metal complexes of Salen(bis(Salicylidene)1,2-ethylenediamine) were carried out at HF and DFT methods employing Lanl2DZ basis set. In this work structural, energies, bond lengths and other physical properties between Mn2+,Cu2+ and Ni2+ ions coordinated by salen–type ligands are examined. All calculations were performed using Gaussian 98W program series. To investigate local aromaticities, NICS were calculated at all centers of rings. The higher the band gap indicating a higher global aromaticity. The possible binding energies have been evaluated. We have evaluated Frequencies and Zero-point energy with freq calculation. The NICS(Nucleous Independent Chemical Shift) Results show Ni(II) complexes are antiaromatic and aromaticites of Mn(II) complexes are larger than Cu(II) complexes. The energy Results show Cu(II) complexes are stability than Mn(II) and Ni(II) complexes.
Abstract: Search for a tertiary substructure that geometrically
matches the 3D pattern of the binding site of a well-studied protein provides a solution to predict protein functions. In our previous work,
a web server has been built to predict protein-ligand binding sites
based on automatically extracted templates. However, a drawback of such templates is that the web server was prone to resulting in many
false positive matches. In this study, we present a sequence-order constraint to reduce the false positive matches of using automatically
extracted templates to predict protein-ligand binding sites. The binding site predictor comprises i) an automatically constructed template library and ii) a local structure alignment algorithm for
querying the library. The sequence-order constraint is employed to
identify the inconsistency between the local regions of the query protein and the templates. Experimental results reveal that the sequence-order constraint can largely reduce the false positive matches and is effective for template-based binding site prediction.
Abstract: Bone growth factors, such as Bone Morphogenic
Protein-2 (BMP-2) have been approved by the FDA to replace grafting for some surgical interventions, but the high dose requirement limits its use in patients. Noggin, an extracellular protein, blocks the effect of BMP-2 by binding to BMP. Preventing
the BMP-2/noggin interaction will help increase the free
concentration of BMP-2 and therefore should enhance its efficacy to
induce bone formation. The work presented here involves
computational design of novel small molecule inhibitory agents of BMP-2/noggin interaction, based on our current understanding of
BMP-2, and its known putative ligands (receptors and antagonists). A
successful acquisition of such an inhibitory agent of BMP-2/noggin interaction would allow clinicians to reduce the dose required of
BMP-2 protein in clinical applications to promote osteogenesis. The
available crystal structures of the BMPs, its receptors, and the binding partner noggin were analyzed to identify the critical residues
involved in their interaction. In presenting this study, LUDI de novo design method was utilized to perform virtual screening of a large
number of compounds from a commercially available library against the binding sites of noggin to identify the lead chemical compounds
that could potentially block BMP-noggin interaction with a high specificity.
Abstract: There is an urgent need to develop novel
Mycobacterium tuberculosis (Mtb) drugs that are active against drug
resistant bacteria but, more importantly, kill persistent bacteria. Our
study structured based on integrated analysis of metabolic pathways,
small molecule screening and similarity Search in PubChem
Database. Metabolic analysis approaches based on Unified weighted
used for potent target selection. Our results suggest that pantothenate
synthetase (panC) and and 3-methyl-2-oxobutanoate hydroxymethyl
transferase (panB) as a appropriate drug targets. In our study, we
used pantothenate synthetase because of existence inhibitors. We
have reported the discovery of new antitubercular compounds
through ligand based approaches using computational tools.
Abstract: This study determines the effect of naked and heparinbased
super-paramagnetic iron oxide nanoparticles on the human
cancer cell lines of A2780. Doxorubicin was used as the anticancer
drug, entrapped in the SPIO-NPs. This study aimed to decorate
nanoparticles with heparin, a molecular ligand for 'active' targeting
of cancerous cells and the application of modified-nanoparticles in
cancer treatment. The nanoparticles containing the anticancer drug
DOX were prepared by a solvent evaporation and emulsification
cross-linking method. The physicochemical properties of the
nanoparticles were characterized by various techniques, and uniform
nanoparticles with an average particle size of 110±15 nm with high
encapsulation efficiencies (EE) were obtained. Additionally, a
sustained release of DOX from the SPIO-NPs was successful.
Cytotoxicity tests showed that the SPIO-DOX-HP had higher cell
toxicity than the individual HP and confocal microscopy analysis
confirmed excellent cellular uptake efficiency. These results indicate
that HP based SPIO-NPs have potential uses as anticancer drug
carriers and also have an enhanced anticancer effect.