title: Molecular Dynamics Investigation of gluazo, a Photo-Switchable Ligand for the Glutamate Receptor GluK2.
abstract: Photochromic ligands (PCLs), defined as photoswitchable molecules that are able to endow native receptors with a sensitivity towards light, have become a promising photopharmacological tool for various applications in biology. In general, PCLs consist of a ligand of the target receptor covalently linked to an azobenzene, which can be reversibly switched between two configurations upon light illumination. Gluazo, as a PCL that targets excitatory amino acid receptors, in its dark-adapted trans iso-form was characterized to be a partial agonist of the kainate glutamate receptor GluK2. Application of UV light leads to the formation of the cis form, with remarkedly reduced affinity towards GluK2. The mechanism of the change of ligand affinity induced by the photoisomerization was unresolved. The presented computational study explains how the isomerization of such a PCL affects the structural changes in the target receptor that lead to its activation.
authors: Department of Theoretical Chemical Biology, Institute of Physical Chemistry, Karlsruhe Institute of Technology, Kaiserstr. 12, 76131, Karlsruhe, Germany.
authors: Yanan
authors: Y
authors: Guo
authors: Department of Theoretical Chemical Biology, Institute of Physical Chemistry, Karlsruhe Institute of Technology, Kaiserstr. 12, 76131, Karlsruhe, Germany.
authors: Tino
authors: T
authors: Wolter
authors: Department of Theoretical Chemical Biology, Institute of Physical Chemistry, Karlsruhe Institute of Technology, Kaiserstr. 12, 76131, Karlsruhe, Germany.
authors: Tomáš
authors: T
authors: Kubař
authors: Department of Chemistry, Ludwig-Maximilians-Universität München and Center of Integrated Protein Science, Butenandtstr. 5-13, 81377 Munich, Germany.
authors: Martin
authors: M
authors: Sumser
authors: Department of Chemistry, Ludwig-Maximilians-Universität München and Center of Integrated Protein Science, Butenandtstr. 5-13, 81377 Munich, Germany.
authors: Dirk
authors: D
authors: Trauner
authors: Department of Theoretical Chemical Biology, Institute of Physical Chemistry, Karlsruhe Institute of Technology, Kaiserstr. 12, 76131, Karlsruhe, Germany.
authors: Marcus
authors: M
authors: Elstner
mesh_terms: D006860:Hydrogen Bonding; D015640:Ion Channel Gating / Q000528:radiation effects; D008024:Ligands; D008027:Light; D056004:Molecular Dynamics Simulation; D055503:Protein Multimerization / Q000528:radiation effects; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D018092:Kainic Acid Receptors / Q000737:chemistry* / Q000378:metabolism*; D013237:Stereoisomerism; D013816:Thermodynamics; D000097806:GluK2 Kainate Receptor
chemical_list: D008024:Ligands; D018092:Kainic Acid Receptors; D000097806:GluK2 Kainate Receptor