Retinyl Chromophore in Visual Rhodopsin

The H and C Nuclear Magnetic Resonance (NMR) spectra of the retinyl chromophore in rhodopsin are investigated by using Quantum Mechanics/Molecular Mechanics (QM/MM) hybrid methods at the Density Functional Theory (DFT) B3LYP/631G*:Amber level, in conjunction with the Gauge Independent Atomic Orbital (GIAO) method for the ab initio Self-Consistent-Field (SCF) calculation of NMR chemical shifts. The study provides a first-principle interpretation of solid-state NMR experiments based on recently developed QM/MM computational models of rhodopsin and bathorhodopsin [Gascón, J.A.; Batista, V.S. (2004) Biophys. J., 87: 2931-2941]. A detailed analysis of nonbonding interactions responsible for inducing NMR chemical shifts characteristic of the rhodopsin and bathorhodopsin ligand-binding sites is presented, with emphasis on the influence of polar residues in the Extracellular loop II and structural water molecules. The reported results are particularly relevant to the development and validation of atomistic models of prototypical G-protein-coupled receptors which regulate signal transduction across plasma membranes.