NMD SERVER: NATURAL MEDICINES DATABASE FOR DRUG DISCOVERY

Cancer is the most frequently diagnosed disease globally and the second leading cause of the death. Natural Medicines are the alternative form of treatment that includes use of various plants. It is one of the safe treatment option to treat cancer and safer than allopathic medicines in order to reduce side effects. NMD Server: Natural Medicines Database for Drug Discovery is a unique and significant database of its kind, giving researchers, medical practitioners, pharmaceutical industries and students of Life Sciences an instant access to over 354 records of Natural Medicines which may be developed and used for treatment of Cancer. This database constitutes the specific information related to Natural Medicines and their respective target sites. NMD Server: Natural Medicines Database for Drug Discovery provides all the information (database fields) regarding the physiological parameters of database and is considered to be the linked table with pre-determined values and names that are included to aid in populating the fields of the linked tables. There have been many different types of fields with its respective data types that have been designated on the basis of data provided. NMDdock Tools have been integrated in this database for convenience for users like docking analysis of target and natural medicine, Sensitivity & Specificity analysis of natural medicine, Linear Correlation and Regression tool, Sequence Manipulation of target, Statistical Analysis. For the precise information about any particular drug, connectivity has been made with other databases and applications based highly bioinformatics tools have been embedded for convenience of users.&nbsp

CPP-ZFN: A potential DNA-targeting anti-malarial drug

<p>Abstract</p> <p>Background</p> <p>Multidrug-resistant <it>Plasmodium </it>is of major concern today. Effective vaccines or successful applications of RNAi-based strategies for the treatment of malaria are currently unavailable. An unexplored area in the field of malaria research is the development of DNA-targeting drugs that can specifically interact with parasitic DNA and introduce deleterious changes, leading to loss of vital genome function and parasite death.</p> <p>Presentation of the hypothesis</p> <p>Advances in the development of zinc finger nuclease (ZFN) with engineered DNA recognition domains allow us to design and develop nuclease of high target sequence specificity with a mega recognition site that typically occurs only once in the genome. Moreover, cell-penetrating peptides (CPP) can cross the cell plasma membrane and deliver conjugated protein, nucleic acid, or any other cargo to the cytoplasm, nucleus, or mitochondria. This article proposes that a drug from the combination of the CPP and ZFN systems can effectively enter the intracellular parasite, introduce deleterious changes in its genome, and eliminate the parasite from the infected cells.</p> <p>Testing the hypothesis</p> <p>Availability of a DNA-binding motif for more than 45 triplets and its modular nature, with freedom to change number of fingers in a ZFN, makes development of customized ZFN against diverse target DNA sequence of any gene feasible. Since the <it>Plasmodium </it>genome is highly AT rich, there is considerable sequence site diversity even for the structurally and functionally conserved enzymes between <it>Plasmodium </it>and humans. CPP can be used to deliver ZFN to the intracellular nucleus of the parasite. Signal-peptide-based heterologous protein translocation to <it>Plasmodium</it>-infected RBCs (iRBCs) and different <it>Plasmodium </it>organelles have been achieved. With successful fusion of CPP with mitochondrial- and nuclear-targeting peptides, fusion of CPP with 1 more <it>Plasmodium </it>cell membrane translocation peptide seems achievable.</p> <p>Implications of the hypothesis</p> <p>Targeting of the <it>Plasmodium </it>genome using ZFN has great potential for the development of anti-malarial drugs. It allows the development of a single drug against all malarial infections, including multidrug-resistant strains. Availability of multiple ZFN target sites in a single gene will provide alternative drug target sites to combat the development of resistance in the future.</p

<i style="">In silico</i> designing of insecticidal small interfering RNA (siRNA) for <i style="">Helicoverpa armigera </i>control

469-474Helicoverpa armigera, a polyphagous lepidopteron insect pest causes severe yield loss in cotton, legumes, tomato, okra and other crops. Application of chemical pesticides although effective, has human health and environmental safety concerns. Moreover, development of resistance against most of the available pesticides is compelling to look for alternative strategies. Adoption of Bt transgenic crops have resulted in reduction in pesticide consumption and increasing crop productivity. However, sustainability of Bt transgenic crops is threatened by the emergence of insect resistance. In the present study potential insecticidal siRNA were identified in six H. armigera hormonal pathway genes. Out of over 2000 computationally identified siRNA, 16 most promising siRNA were selected that address the biosafety concerns and have high potential of targeted gene silencing. These siRNA will be useful for chemical synthesis, in insect feeding assays and knockdown the target H. armigera hormone biosynthesis, consequently obstructing the completion of insect life cycle. The siRNA have a great potential of deployment to control H. armigera alone as well as with Bt for insect resistance management

Enzyme selectivity of new cyclooxygenase-2/5 lipoxygenase inhibitors using molecular modeling approach

86-96We have studied the conformational flexibility of three 5-keto-substituted 7-tert-butyl-2,3-dihydro-3,3-dimethylbenzofurans (DHDMBFs) which show dual cyclooxygenase (COX) and 5-lipoxygenase (LOX) inhibition and are potential candidates as antiinflammatory agents and analgesics. The conformations were studied by systematic search, molecular mechanics (MM) and simulated annealing molecular dynamics (SAMD) technique have also studied several structure based parameters and distribution of molecular electrostatic potential (MEP) around these molecules. All the three compounds were docked in the active cavity of cyclooxygenase-2 (COX-2) using graphical and energy grid search techniques. The complex geometries were optimized by MM. The results on conformation al flexibility, inter-atomic distances and angles, MEP distribution and points of contacts with peptide side chains in active cavity have been used to understand the mechanistic cause of differential action of these molecules

Insights into unbound–bound states of GPR142 receptor in a membrane-aqueous system using molecular dynamics simulations

<p>G protein coupled receptors (GPCRs) are source machinery in signal transduction pathways and being one of the major therapeutic targets play a significant in drug discovery. GPR142, an orphan GPCR, has been implicated in the regulation of insulin, thereby having a crucial role in Type II diabetes management. Deciphering of the structures of orphan, GPCRs (O-GPCRs) offer better prospects for advancements in research in ion translocation and transduction of extracellular signals. As the crystallographic structure of GPR142 is not available in PDB, therefore, threading and <i>ab initio</i>-based approaches were used for 3D modeling of GPR142. Molecular dynamic simulations (900 ns) were performed on the 3D model of GPR142 and complexes of GPR142 with top five hits, obtained through virtual screening, embedded in lipid bilayer with aqueous system using OPLS force field. Compound 1, 3, and 4 may act as scaffolds for designing potential lead agonists for GPR142. The finding of GPR142 MD simulation study provides more comprehensive representation of the functional properties. The concern for Type II diabetes is increasing worldwide and successful treatment of this disease demands novel drugs with better efficacy.</p

Receptor thermodynamics of ligand–receptor or ligand–enzyme association

Experimental techniques that directly assess the thermodynamics of ligand–receptor or ligand–enzyme association, such as isothermal titration calorimetry, have been improved in recent years and can provide thermodynamic details of the binding process. Parallel to the continuous increase in computational power, several classes of computational methods have been developed that can be used to get a more detail insight into the mode and affinity of compounds (drug) to their target (off). Such methods are affiliated with a qualitative and/or quantitative assessment of binding free energies, and differently trade off speed versus physical accuracy. With the current wealth of available three-dimensional structures of proteins and their complexes with ligands, structure-based drug design studies can be used to identify the key ligand interactions and free energy calculations, and can quantify the thermodynamics of binding between ligand and the target of interest