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A Ligand Channel through the G Protein Coupled Receptor Opsin 1. 1. 1 2 1 Peter W. Hildebrand *, Patrick Scheerer , Jung Hee Park , Hui-Woog Choe , Ronny Piechnick , 1 1 1 Oliver P. Ernst , Klaus Peter Hofmann , Martin Heck ¨ ´ ¨ 1 Institut fur Medizinische Physik und Biophysik, Charite - Universitatsmedizin Berlin, Berlin, Germany, 2 Department of Chemistry College of Natural Science, Chonbuk National University, Chonju, South Korea Abstract The G protein coupled receptor rhodopsin contains a pocket within its seven-transmembrane helix (TM) structure, which bears the inactivating 11-cis-retinal bound by a protonated Schiff-base to Lys296 in TM7. Light-induced 11-cis-/all-trans - isomerization leads to the Schiff-base deprotonated active Meta II intermediate. With Meta II decay, the Schiff-base bond is hydrolyzed, all-trans-retinal is released from the pocket, and the apoprotein opsin reloaded with new 11-cis-retinal. The crystal structure of opsin in its active Ops* conformation provides the basis for computational modeling of retinal release and uptake. The ligand-free 7TM bundle of opsin opens into the hydrophobic membrane layer through openings A (between TM1 and 7), and B (between TM5 and 6), respectively. Using skeleton search and molecular docking, we find a continuous channel through the protein that connects these two openings and comprises in its central part the retinal