Abstract:

Rhodopsin is a membrane protein and its retinal (RET) active binding sites are related to the process of vision and the pathology of some ophthalmic ailments. Based on the bovine rhodopsin crystal structure (PDB code: 1U19), computations were performed using density functional theory to explore the interaction and binding energies between the RET-Lys296 residue and each of the 30 amino acid residues arranged in a sphere with 0.6 nm radius around a RET molecule. Results show that Glu113, Glu181 and Glu122 residues are the active binding sites for the protonated RET-Lys296 residue and that their binding energies are -333.38, -205.67 and -194.56 kJ·mol-1, respectively. They each have one negative charge to interact with the protonated RET-Lys296 residue through a strong electrostatic interaction. Other residues Ala292, Cys187, Phe293, Pro291 and Trp265 have smaller binding energies with the protonated RET-Lys296 residue at the 1U19 protein. When the RET-Lys296 residue is deprotonated, the interactions mentioned above disappear therefore to promote the dissociation of retinal from rhodopsin. Our results demonstrate that two crystal H2O molecules that form hydrogen bonds to Glu113 and Glu181 residues also play an important role in stabilizing the RET-Lys296 residue.

Key words: Rhodopsin, Retinal, 1U19, Active site, Density functional theory