The interaction of the 11-cis-retinal chromophore with the surrounding amino acid residues in the chromophore center of the rhodopsin protein has been investigated for the E181K mutant form using molecular dynamics simulation. A comparative analysis of the arrangement of the amino acid residues in the chromophore center has been performed for both wild (native) and mutant rhodopsins. It is shown that for the E181K mutant rhodopsin there is no proper binding of 11-cis-retinal with the surrounding amino acid residues. The distortion of the conformation states in the mutant rhodopsin molecule takes place in both the chromophore center and cytoplasmic domain. Our simulations suggest that a stable covalent linkage of 11-cis-retinal with the protein part (viz. opsin) of the rhodopsin molecule will not form. This, on the other hand, implies that the protein's active site in the cytoplasmic domain, which is responsible for the G-protein binding (so-called transducin), may not be completely blocked. Based on our molecular simulation data, we discuss the possible correlation between retinitis pigmentosa pathogenesis and the structural and functional properties of the rhodopsin protein.
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