Computer Simulation Of The Biological Mechanism Of Rhodopsin

As a structural prototype for the study of G-protein coupled receptor(GPCR),Rhodopsin is currently perhaps the best-studied system among the class of GPCRs. It is a light-sensitive receptor protein involved in visual phototransduction. The protein consists of opsin protein moieties and 11-cis retinal covalently bound via a protonated Schiff base linkage to Lys-296. The activation mechanism of rhodopsin has not been fully elucidated. It needs to be deeply studied to understand this mechanism, in order to lay the groundwork to the development of drug research and development in the treatment of diseases related to vision (Retinitis pigmentosa).In this paper, a retinal geometry was selected as researching object based on the theory of quantum chemistry. In order to analyze their structural characteristics and spectral properties, the Gaussian software package was used to build the 11-cis retinal and all-trans retinal deprotonated Schiff base molecule. The obtained results are summarized as follows:1. B3LYP/6-311++G(d,p) level of theory was carried out to explain the isomerization process of retinal stereoisomers based on the structural and molecular properties in gas and aqueous phase. The energy barriers, dipole moments, bond orders,HOMO-LUMO energy gaps, and theoretically predicted vibrational frequencies of the retinal isomers were analyzed. The influence of the implicit aqueous environment on the geometry of polyene chain and the vibrational spectra of retinal isomers were evident. The geometries of 11-cis and all-trans retinal isomers exhibited delocalized bonds along the polyene chain in the aqueous phase with a pattern of longer double bonds and shorter single bonds. Moreover, the vibrational frequencies of the retinal isomers calculated at the B3LYP level of theory were in better agreement with the experimental values. The method and results obtained in this work may provide a theoretical basis to study this isomerization process in explicit aqueous environment,even in the protein environment.2. The B3LYP/6-31++G(d,p) level of theory was used to carry out a conformational space analysis of the all-trans retinal deprotonated Schiff base molecule.Eight conformers in total, selected on the basis of the potential energy surface exploration corresponding to the four internal backbone torsion angles. The standard split-valence 6-311++G(d,p) basis set in combination with MP2 and B3LYP levels were carried out to analyze the structural characteristics and spectral properties of the conformers. Results presented in this paper showed that the relative stability order of the conformers might be independent of the level of theory used. It was also reconfirmed that the TD-DFT method would systematically underestimate the excitation energy. The characteristic peak nearby 1600 cm-1 corresponding to the ECC mode (in-phase collective motion of the C=C stretching) could be notably observed from the predicted Raman spectrum. Moreover, it is suggested that B3LYP level may be a proper choice for theoretically study of Raman spectrum, concerning the polyene conjugated systems.