Essential Dynamics of mGluR5 ATD : extracting large concerted motions from protein molecular dynamics trajectories

Essential Dynamics of mGluR5 ATD : extracting large concerted motions from protein molecular dynamics trajectoriesEight members of the G-protein coupled metabotropic glutamate receptor family have been identified (mGluR1-8) and have been divided on the basis of sequence omology, second messenger coupling and pharmacology into three groups. The group I appear to offer considerable therapeutic potential. Particularly mGluR5 antagonists exhibit anxiolytic activity in a broad range of preclinical models at doses whixh do not affect spontaneous locomotor activity. mGluR5 have also been implicated in the development of dependence to psychostimulants and other drugs of abuse. In this work the sequence of the amino terminal domain of mGluR5 was modelled on the Xray structuire of mGluR1 complexed with glutamate. Results are reported.