Current Issue : January - March Volume : 2012 Issue Number : 1 Articles : 11 Articles
Metalloprotease enzyme play an important role in tissue remolding associated with various process such as morphogenesis, angiogenesis, tissue repair, arthritis and metastasis. In cancer elaboration of metalloprotease takes place . In present study the docking study was performed on 14 Schiff bases of dapsone and their substituted 2-azetidinone with metalloprotease enzyme. The binding conformation of Schiff bases of dapsone and their substituted 2-azetidinone for the inhibition of metalloprotease enzyme for predicting the role of dapsone and their derivative as new potential inhibitors useful as anticancer agent was performed by using Molegro Virtual Docker MVD (Molegro Aps). The binding was determined and predicted by molecular docking. Best docking scores were shown by molecule 1a and 2c....
Over the last decade, and especially after the advent of fluorescent in situ hybridization imaging and chromosome conformation capture methods, the availability of experimental data on genome three-dimensional organization has dramatically increased. We now have access to unprecedented details of how genomes organize within the interphase nucleus. Development of new computational approaches to leverage this data has already resulted in the first three-dimensional structures of genomic domains and genomes. Such approaches expand our knowledge of the chromatin folding principles, which has been classically studied using polymer physics and molecular simulations. Our outlook describes computational approaches for integrating experimental data with polymer physics, thereby bridging the resolution gap for structural determination of genomes and genomic domains....
Natural product gain noteworthy attention as pharmaceuticals and amongst them Chalcone present excellent pharmaceutical profile as influenza virus inhibitors. Considering this fact, we have docked one of the chalcone isolated from Glycyrrhiza inflata. Docking results divulge that the most active chalcone bind with H1N1 receptor by hydrogen bonding, hydrophobic and polar interactions....
Pyrazinamidase (PncA) activates the first-line antituberculous drug pyrazinamide into pyrazinoic acid. The crystal structure of the Mycobacterium tuberculosis PncA protein has been determined, showing significant differences in the substrate binding cavity when compared to the pyrazinamidases from Pyrococcus horikoshii and Acinetobacter baumanii. In M. tuberculosis, this region was found to hold a Fe2+ ion coordinated by one aspartate and three histidines, one of them corresponding to His57 which is replaced by Asp in Mycobacterium bovis, a species naturally resistant to pyrazinamide. The binding cavity also contains a Cys138-Asp8-Lys96 motif evocating a cysteine-based catalytic mechanism. Mutants have been constructed and investigated by kinetic and thermal shift assays, highlighting the importance of protein folding and thermal stability in the pyrazinamidase activity....
Cyclooxygenase come into sight as one of the important target for noval anti-inflammatory agents. The present study aims to reveal characteristic binding mechanism of SC-75416 and SD-8381. The SC-75416 interacts with cox-2 in a stereochemical way in which existence of enantiomerism plays crucial role. The orientation SC-75416 in cox-2 binding pocket was governed by different enantiomeric forms whereas no such binding mechanism was reported for SD-8381....
The natural isoquinoline alkaloid berberine possesses potential to treat Alzheimer's disease (AD) by targeting multiple pathogenic factors. In the present study, docking simulations were performed to gain deeper insights into the molecular basis of berberine's inhibitory effects against the important pathogenic enzymes of AD, that is, acetylcholinesterase, butyrylcholinesterase, and two isoforms of monoamine oxidase. It was found that the theoretical binding affinities of berberine to the four enzymes are very close to the experimental values, which verify the methodology. Further inspection to the binding modes found that hydrophobic interactions between the hydrophobic surface of berberine and neighboring hydrophobic residues are the principal forces contributing to the ligand-receptor interactions. Although berberine cation also has potential to form electrostatic interaction with neighboring residues, it is interesting to find that electrostatic force is excluded in the four cases unexpectedly. These results have important implications for the berberine-based anti-AD drug design....
INX-08189 is (E)-3-(4-hydroxy-2-methoxyphenyl)-1-(4-hydroxyphenyl) prop-2-en-1-one is clinical trial drug candidate for hepatitis C virus. In this study, we are presenting possible binding mechanism of said candidate by docking simulation. The study divulge that, INX-08189 bind with viral protein by arene-arene, arene-cation and hydrophobic interactions. It is noted that, INX-8189 acquire different conformation in receptor pocket by exhibiting different enantiomeric forms....
A structural rationale for recent emergence of azole (imidazole and triazole) resistance associated with CYP51 mutations in the wheat pathogen Mycosphaerella graminicola is presented, attained by homology modelling of the wild type protein and 13 variant proteins. The novel molecular models of M. graminicola CYP51 are based on multiple homologues, individually identified for each variant, rather than using a single structural scaffold, providing a robust structure-function rationale for the binding of azoles, including important fungal specific regions for which no structural information is available. The wild type binding pocket reveals specific residues in close proximity to the bound azole molecules that are subject to alteration in the variants. This implicates azole ligands as important agents exerting selection on specific regions bordering the pocket, that become the focus of genetic mutation events, leading to reduced sensitivity to that group of related compounds. Collectively, the models account for several observed functional effects of specific alterations, including loss of triadimenol sensitivity in the Y137F variant, lower sensitivity to tebuconazole of I381V variants and increased resistance to prochloraz of V136A variants. Deletion of Y459 and G460, which brings about removal of that entire section of beta turn from the vicinity of the binding pocket, confers resistance to tebuconazole and epoxiconazole, but sensitivity to prochloraz in variants carrying a combination of A379G I381V ?Y459/G460. Measurements of binding pocket volume proved useful in assessment of scope for general resistance to azoles by virtue of their accommodation without bonding interaction, particularly when combined with analysis of change in positions of key amino acids. It is possible to predict the likely binding orientation of an azole molecule in any of the variant CYPs, providing potential for an in silico screening system and reliable predictive approach to assess the probability of particular variants exhibiting resistance to particular azole fungicides....
Type-2 ribosome-inactivating proteins, composed of a toxic A-chain and lectin-like B-chain, display various biological functions, including cytotoxicity and immunomodulation. We here cloned the lectin-like B-chain encoding fragment of a newly identified type-2 RIP gene, articulatin gene, from Viscum articulatum, into a bacterial expression vector to obtain nonglycosylated recombinant protein expressed in inclusion bodies. After purification and protein refolding, soluble refolded recombinant articulatin B-chain (rATB) showed lectin activity specific toward galactoside moiety and was stably maintained while stored in low ionic strength solution. Despite lacking glycosylation, rATB actively bound leukocytes with preferential binding to monocytes and in vitro stimulated PBMCs to release cytokines without obvious cytotoxicity. These results implicated such a B-chain fragment as a potential immunomodulator....
We investigated the 16?-hydroxylation of steroid molecules and regioselective binding mode in homology-modeled cytochrome\nP450-2C11 to correlate the biological study with the computational molecular modeling. It revealed that there was a positive\nrelationship between the observed inhibitory potencies and the binding free energies. Docking of steroid molecules into this\nhomology-modeled CYP2C11 indicated that 16?-hydroxylation is favored with steroidal molecules possessing the following\ncomponents, (1) a bent A-B ring configuration (5?-reduced), (2) C-3 ?-hydroxyl group, (3) C-17?-acetyl group, and (4) methyl\ngroup at both the C-18 and C-19. These respective steroid components requirements were defined as the inhibitory contribution\nfactor. Overall studies of the male rat CYP2C11 metabolism revealed that the above-mentioned steroid components requirements\nwere essential to induce an effective inhibition of [3H]progesterone 16?-hydroxylation. As far as docking of homology-modeled\nCYP2C11 against investigated steroids is concerned, they are docked at the active site superimposed with flurbiprofen. It was also\nfound that the distance between heme iron and C16?-H was between 4 to 6 ?A and that the related angle was in the range of\n180 �± 45?....
The human immunodeficiency virus (HIV) is the etiologic agent of AIDS. L-735,524:P is a clinical trial candidate designed to inhibit HIV protease enzyme. The objective of the study is to predict the mechanism of L-735,524:P in HIV protease inhibition by molecular docking. Piperazine ring of L-735,524:P elicit hydrogen bonding with Asp B25. Here protonated nitrogen of piperazine acts as hydrogen bond donor and form hydrogen bond with both acceptor atom of AspB25. Furthermore 2 hydroxyl group of inden ring exhibit hydrogen bonding with ArgA8. L-735,524:P align horizontally in the receptor cage where we have observed some stereochemical aspects like presence of various chiral centers. These chiral centers may facilitate inhibition of HIV protease. The present docking analysis conclude that compound L-735,524:P inhibit HIV protease enzyme by interacts with HIV protease by hydrogen bonding, hydrophobic and polar interactions...
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