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This study focuses on structural features of a particular GPCR type, the family C GPCRs. Structure- and ligand-based approaches were adopted for prediction of novel mGluR5 binding ligand and their binding modes. The objectives of this study were: 1. An analysis of function and structural implication of amino acids in the TM region of family C GPCRs. 2. The prediction of the TM domain structure of mGluR5. 3. The discovery of novel selective allosteric modulators of mGluR5 by virtual screening. 4. The prediction of a ligand binding mode for the allosteric binding site in mGluR5. GPCRs are a super-family of structurally related proteins although their primary amino acid sequence can be diverse. Using sequence information a conservation analysis of family C GPCRs should be applied to reveal characteristic differences and similarities with respect function, folding and ligand binding. Using experimental data and conservation analysis the allosteric binding site of mGluR5 should be characterized regarding NAM and PAM and selective ligand binding. For further evaluation experimental knowledge about family A GPCRs as well as conservation between vertebrate rhodopsins was planned to be compared to results obtained for family C GPCRs (Section 4.1 Conservation analysis of family C GPCRs). Since no receptor structure is available for any family C GPCR, discussion of conserved sequence positions between family A and C GPCRs requires the prediction of a receptor structure for mGluR5 using a family A receptor as template. In order to predict the mGluR5 structure a sequence alignment to a GPCR template protein will have to be proposed and GPCR specific features considered in structure calculation (Section 4.1.4 Structure prediction of mGluR5). The obtained structure was intended to be involved in ligand binding mode prediction of newly discovered active molecules. For discovery of novel selective mGluR modulators several ligand-based virtual screening protocols were adapted and evaluated. Prediction models were derived for selection of possibly active molecules using a diverse collection of known mGluR binding ligands. For that purpose a data collection of known mGluR binding ligands should be established and this reference collection analyzed with respect to different ligand activity classes, NAM or PAM and selective modulators. The prediction of novel NAMs and PAMs using several combinations of 2D-, 3D-, pharmacophore or molecule shape encoding methods with machine learning techniques and similarity determining methods should be tested in a prospective manner (Section 4.2 Virtual screening for novel mGluR modulators). In collaboration with Merz Pharmaceuticals (Merz GmbH & Co. KGaA, Frankfurt am Main, Germany) the modulating effect of a few hundred molecules should be approved in a functional cell-based assay. With the objective to predict a binding mode of the discovered active molecules, molecule docking should be applied using the allosteric binding site of the modeled mGluR5 structure (Section 4.2.4 Modeling of binding modes). Predicted ligand binding modes are to be correlated to conservation profiles that had resulted from the sequence-based entropy analysis and information from mutation experiments, and shall be compared to known ligand binding poses from crystal structures of family A GPCRs.
We first report from the 5th Dry Grassland Meeting held from 28th to 30st of August 2008 in Kiel, Germany. Then we take stock of the achievements of the German Arbeitsgruppe Trockenrasen and the international Working Group on Dry Grasslands in the Nordic and Baltic Region towards establishment of vegetation databases of dry grasslands in these study regions. At the conference, the European Dry Grassland Group (EDGG) was founded as an international platform of dry grassland researchers and conservationists. As networking tools it provides a homepage on the internet, publishes a quarterly electronical bulletin, and will organise the future European Dry Grassland Meetings. In the last part of this contribution, we give a short introduction to the five articles of this Special Feature. Four of them make a major contribution to supra-national classification of Koelerio-Corynephoretea and Festuco- Brometea communities, respectively, by providing syntaxonomic overviews based on comprehensive data from eastern European countries for which only few data have been available until now. The other major focus of the Feature papers is on degradation and restoration of various types of dry grasslands.
This paper presents the results of a study on psammophilous grasslands, conducted during the years 1994-1997 and in 2008 in the Masurian Lake District (NE Poland). The study aimed at the determination of floristic composition, phytosociological diversity and habitat characteristics. Field work resulted in 511 phytosociological releves. Soil samples were taken to determine pH, hydrolytic acidity, sum of basic cations, cation exchange capacity, content of CaC03 and total carbon. In 2008, the presence of communities dominated by grey-hair grass (Corynephorus canescens) in the previously established sites was checked. TWINSPAN was used for hierarchic classification of the association Comiculario aculeatae-Corynephoretum canescentis (syn. Spergulo morisonii-Corynephoretum canescentis). Accordingly, the association is divided into four subtypes (typical subtype, subtype with Cladonia mitis, subtype with Thymus serpyllum and subtype with Festuca ovina) with nine variants. Field observations showed that the communities analyzed have been under strong anthropogenic pressure, causing their degeneration and decrease in area. The most common human uses of psammophilous grassland communities are housing development, road construction, afforestation, sand extraction, wood storage and unauthorized dumping. In contrast to the above types of land use, seasonal use of grasslands for recreation purposes (as sunbathing spots or as sports fields) does not lead to their degeneration and may have a beneficial influence on their maintenance as a component of the local landscape.