The nature of the complex counterion of the chromophore in rhodopsin

The interaction of the rhodopsin chromophore with different complex counterions has been investigated using density functional theory methodology for both energy minimization and molecular dynamics calculations. The initial geometry of the retinal chromophore attached to Lys296 and of other amino acid residues close to the retinal binding site was taken from the rhodopsin X-ray structure by Palczewski et al. We also considered the presence of one water molecule (Wat2b) found in a recent study by Okada et al. The following counterions were studied (in order of increasing complexity): Glu113; Glu113 and Thr94; Glu113 and Wat2b; Glu113, Thr94, and Wat2b; Glu113, Thr94, Wat2b, and Cysl87. With glutamate only, the protonated chromophore is not stable, and the proton is shifted rapidly to the glutamate counterion. Thr94 stabilizes the protonated chromophore by engaging the oxygen of Glu113 in hydrogen bonding. Wat2b works by the same mechanism, though the effect is weaker, and the chromophore oscillates between the protonated and the deprotonated state. The additional Cys187 does not change the essential features of this complex. The special stabiiizing role of Thr94 is traced back to the stereochemical arrangement of the proton donor relative to Glu113.