450fd811e15aad429b89ba9213797215 pmc_30897742.pdf 9dac787b6fb225f0e750d7c1ff1aee82cba82bd5 pmc_30897742.pdf 201ae4ad2cd0262321df1e28af3b56df55eaeb844e529507864471d997dee235 pmc_30897742.pdf Title: Computational Drug Design Applied to the Study of Metabotropic Glutamate Receptors Subject: Metabotropic glutamate (mGlu) receptors are a family of eight GPCRs that are attractive drug discovery targets to modulate glutamate action and response. Here we review the application of computational methods to the study of this family of receptors. X-ray structures of the extracellular and 7-transmembrane domains have played an important role to enable structure-based modeling approaches, whilst we also discuss the successful application of ligand-based methods. We summarize the literature and highlight the areas where modeling and experiment have delivered important understanding for mGlu receptor drug discovery. Finally, we offer suggestions of future areas of opportunity for computational work. Keywords: mGlu; mGluR; homology model; virtual screening; molecular dynamics; allosteric modulator; GPCR; ligand-based design; structure-based design Author: Claudia Llinas del Torrent, Laura Pérez-Benito and Gary Tresadern Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.18 CreationDate: Wed Mar 20 08:34:52 2019 CET ModDate: Wed Mar 20 08:34:52 2019 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 22 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 4855391 bytes Optimized: no PDF version: 1.5 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- XJBHWF+URWPalladioL-Ital Type 1 Custom yes yes no 86 0 MKZKLS+URWPalladioL-Bold Type 1 Custom yes yes no 87 0 BTFGED+VnURWPalladioL-Bold Type 1 Custom yes yes no 88 0 NMKIBT+URWPalladioL-Roma Type 1 Custom yes yes no 89 0 YFNERV+VnURWPalladioL Type 1 Custom yes yes no 90 0 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