Many studies show involvement of metabotropic glutamate receptors (mGluRs) in synaptic excitation transduction. The mGluR family consists of eight proteins divided into three groups corresponding to sequence similarities, pharmacology and physiological role. These groups are: I (mGluR1, -5), II (mGluR2, -3) and III (mGluR4, -6, -7, -8). Group II lies in field of our interest due to its potential as therapeutic target for stroke and pain drugs. Primary goal of our research is to describe a binding mode of positive modulators within a transmembrane part of mGluR2, and to develop a viable virtual model of investigated receptor, so it can be used for further studies.

The lack of crystal structure of transmembrane domain of mGluR2 caused that our approach is based on homology modeling. MGluRs are part of superfamily of G protein coupled receptors (GPCRs) and thus their sequence is similar to Rhodopsin, which crystal structure has been published in PDB database. Rhodopsin structure has been used as a template for homology modeling of mGluR2 receptor. 400 conformers have been generated as a base for molecular docking of selected ligands. As a first step in developing mGluR2 ligand binding mode several high affinity  modulators were intensively docked with various pharmacophoric constrains. The best models will be used for virtual screening of our chemical database and for a complete description of interactions of modulators within transmembrane binding site.

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1. Interaction fingerprints patterns. Binding mode analysis of mGlu2 receptor model based on docking studies