Light-Driven Proton, Sodium Ion, and Chloride Ion Transfer Mechanisms in Rhodopsins: SAC-CI Study.

Bacteriorhodopsin (BR) and halorhodopsin (HR) are well-known light-driven ion-pumping rhodopsins. BR transfers a proton from the intracellular medium to the extracellular medium. HR takes in chloride ion from the extracellular medium. A new light-driven sodium ion-pumping rhodopsin was discovered in 2013 by Inoue, Kandori, and co-workers ( Nat. Commun . 2013 , 4 , 1678 ). The purpose of this article is to elucidate the proton, sodium ion and chloride ion transfer mechanisms and the geometrical changes of the intermediates. The absorption maxima of three rhodopsins were calculated by the SAC/SAC-CI method using the QM/MM optimized geometries. For BR, the SAC-CI results supported the previously proposed proton-transfer mechanism; (1) the photoisomerization from all-trans to 13-cis retinal (K intermediate), (2) the relaxation of the retinal structure (L intermediate), (3) the proton transfer from the Schiff base to the counterion residue (ASP85) (M intermediate), (4) the proton transfer from the ASP96 to the Schiff base (N intermediate), and (5) the thermal isomerization from 13-cis to all-trans retinal (O intermediate). The proton releases to the extracellular medium through the ASP96, the Schiff base, the ASP85, and the GLU204 or GLU194 from the intracellular medium. Furthermore, it clarified that the guanidine group rotation of ARG82 changes the excitation energies of the L and N intermediates, but the effect is small for the resting state and the K, M, and O intermediates. The theoretical calculations suggested that the ARG82 rotation occurs in the N intermediate from the comparison between the experimental absorption spectra and the theoretical excitation energies. For the KR2, the Kandori group proposed the sodium ion transfer mechanism; (1) the photoisomerization from all-trans to 13-cis retinal (K intermediate), (2) the relaxation of the retinal structure (L intermediate), (3) the proton transfer from the Schiff base to the counterion residue (ASP116) (M intermediate), (4) the sodium ion passes through the cavity formed by the rotation of the counterion residue (ASP116) (O intermediate) and (5) the proton of the ASP116 reassociates to the Schiff base. The steps (1) to (3) are the same as ones of BR. The SAC-CI results supported the proposed sodium ion transfer mechanism and suggested that the sodium ion transfer proceeds in the O intermediate as follows; (1) the sodium ion connects with the Schiff base in the cavity formed by the ASP116 rotation, (2) at the same time that the sodium ion passes through the Schiff base, the Schiff base forms the hydrogen bond to the proton of ASP116, and (3) at the same time that the sodium ion transfers to the extracellular medium, the proton reassociates with the Schiff base from the ASP116. Furthermore, our results indicated that the retinal is not all-trans but 13-cis when the sodium ion passes through the Schiff base in the O intermediate. For the HR, since the counterion residue is replaced by the THR126, the proton dose not transfer from the Schiff base. Instead, the chloride ion transfers in the opposite direction to the proton of BR and the sodium ion of KR2. The SAC-CI results supported the previously proposed chloride ion transfer mechanism; (1) the photoisomerization from all-trans to 13-cis retinal (K intermediate), (2) the relaxation of the retinal structure (L intermediate), (3) the chloride ion passes through the Schiff base from the extracellular medium side to the intracellular medium side (N intermediate) and (4) the chloride ion transfer from the Schiff base to the intracellular medium and the thermal isomerization from 13-cis to all-trans retinal (O intermediate). Furthermore, our results suggested that the Schiff base forms bonds to the hydroxide ion instead of the chloride ion in the O intermediate. The negative ion is necessary to keep the total charge around the Schiff base in the O intermediate.

Photoelectron spectrum of NO2 - : SAC-CI gradient study of vibrational-rotational structures.

Three-dimensional accurate potential energy surfaces around the local minima of NO2 - and NO2 were calculated with the SAC/SAC-CI analytical energy gradient method. Therefrom, the ionization photoelectron spectra of NO2 - , the equilibrium geometries and adiabatic electron affinity of NO2 , and the vibrational frequencies including harmonicity and anharmonicity of NO2 - and NO2 were obtained. The calculated electron affinity was in reasonable agreement with the experimental value. The SAC-CI photoelectron spectra of NO2 - at 350 K and 700 K including the rotational effects were calculated using the Franck-Condon approximation. The theoretical spectra reproduced well the fine experimental photoelectron spectra observed by Ervin et al. (J. Phys. Chem. 1988, 92, 5405). The results showed that the ionizations from many vibrational excited states as well as the vibrational ground state are included in the experimental photoelectron spectra especially at 700 K and that the rotational effects are important to reproduce the experimental photoelectron spectra of both temperatures. The SAC/SAC-CI theoretical results supported the analyses of the spectra by Ervin et al., except that we could show some small contributions from the asymmetric-stretching mode of NO2 - . © 2018 Wiley Periodicals, Inc.

Accuracy of Td-DFT in the Ultraviolet and Circular Dichroism Spectra of Deoxyguanosine and Uridine.

Accuracy of the time-dependent density functional theory (Td-DFT) was examined for the ultraviolet (UV) and circular dichroism (CD) spectra of deoxyguanosine (dG) and uridine, using 11 different DFT functionals and two different basis sets. The Td-DFT results of the UV and CD spectra were strongly dependent on the functionals used. The basis-set dependence was observed only for the CD spectral calculations. For the UV spectra, the B3LYP and PBE0 functionals gave relatively good results. For the CD spectra, the B3LYP and PBE0 with 6-311G(d,p) basis gave relatively permissible result only for dG. The results of other functionals were difficult to be used for the studies of the UV and CD spectra, though the symmetry adapted cluster-configuration interaction (SAC-CI) method reproduced well the experimental spectra of these molecules. To obtain valuable information from the theoretical calculations of the UV and CD spectra, the theoretical tool must be able to reproduce correctly both of the intensities and peak positions of the UV and CD spectra. Then, we can analyze the reasons of the changes of the intensity and/or the peak position to clarify the chemistry involved. It is difficult to recommend Td-DFT as such tools of science, at least from the examinations using dG and uridine.

Similarities and Differences between RNA and DNA Double-Helical Structures in Circular Dichroism Spectroscopy: A SAC-CI Study.

The helical structures of DNA and RNA are investigated experimentally using circular dichroism (CD) spectroscopy. The signs and the shapes of the CD spectra are much different between the right- and left-handed structures as well as between DNA and RNA. The main difference lies in the sign at around 295 nm of the CD spectra: it is positive for the right-handed B-DNA and the left-handed Z-RNA but is negative for the left-handed Z-DNA and the right-handed A-RNA. We calculated the SAC-CI CD spectra of DNA and RNA using the tetramer models, which include both hydrogen-bonding and stacking interactions that are important in both DNA and RNA. The SAC-CI results reproduced the features at around 295 nm of the experimental CD spectra of each DNA and RNA, and elucidated that the strong stacking interaction between the two base pairs is the origin of the negative peaks at 295 nm of the CD spectra for both DNA and RNA. On the basis of these facts, we discuss the similarities and differences between RNA and DNA double-helical structures in the CD spectroscopy based on the ChiraSac methodology.

Indicator of the Stacking Interaction in the DNA Double-Helical Structure: ChiraSac Study.

The double-helical structures of DNA are experimentally distinguished by the circular dichroism (CD) spectra. The CD spectra are quite different between the left- and right-handed double-helical structures of DNA. The lowest peak is negative for the left-handed Z-DNA but positive for the right-handed B-DNA. Using the Z-DNA model with a strong stacking interaction, we examined whether the CD spectra depend on the distance between the two base pairs, deoxy-guanosine (dG) and deoxy-cytidine (dC). The result showed that the feature of the SAC-CI CD spectra changes from Z-DNA to B-DNA when increasing the distance between the two base pairs. Therefore, we concluded that the stacking interaction is the origin of the lowest negative peak, being the feature of the CD spectra of Z-DNA, and at the same time that the lack of the negative peak at about 290-300 nm of the CD spectra of B-DNA is due to the weak stacking interaction in B-DNA.

Circular dichroism spectra of uridine derivatives: ChiraSac study.

The experimental circular dichroism (CD) spectra of uridine and NH2-uridine that were different in the intensity and shape were studied in the light of the ChiraSac method. The theoretical CD spectra at several different conformations using the symmetry-adapted-cluster configuration-interaction (SAC-CI) theory largely depended on the conformational angle, but those of the anti-conformers and the Boltzmann average reproduced the experimentally obtained CD spectra of both uridine and NH2-uridine. The differences in the CD spectra between the two uridine derivatives were analyzed by using the angle θ between the electric transition dipole moment (ETDM) and the magnetic transition dipole moment (MTDM).

Conformational dependence of the circular dichroism spectrum of α-hydroxyphenylacetic acid: a ChiraSac study.

The conformational dependence of the circular dichroism (CD) spectrum of a chiral molecule, α-hydroxyphenylacetic acid (HPAA) containing phenyl, COOH, OH and H groups around a chiral carbon atom, has been studied theoretically by using the SAC-CI (symmetry adapted cluster-configuration interaction) theory. The results showed that the CD spectrum of HPAA depends largely on the rotations (conformations) of the phenyl and COOH groups around the single bonds. The first band is due to the excitation of electrons belonging to the phenyl region and therefore sensitive to the phenyl rotation. The second band is due to the excitation of electrons belonging to the COOH region and therefore sensitive to the COOH rotation. From the comparison of the SAC-CI CD spectra calculated at various conformations of phenyl, COOH, and OH groups with the experimental spectrum, we could predict the stable geometry of this molecule, which agreed well with the most stable conformation deduced from the energy criterion. We also calculated the Boltzmann averaged spectrum and obtained better agreement with the experiment. Further, we performed preliminary investigations of the temperature dependence of the CD spectrum of HPAA. In general, the CD spectra of chiral molecules are very sensitive to low-energy processes like the rotations around the single bonds. Therefore, one should be able to study the natures of the weak interactions by comparing the SAC-CI spectra calculated at different geometries and conditions with the experimental spectrum using a new methodology we have termed ChiraSac.

Helical structure and circular dichroism spectra of DNA: a theoretical study.

The helical structure is experimentally determined by circular dichroism (CD) spectra. The sign and shape of the CD spectra are different between B-DNA with a right-handed double-helical structure and Z-DNA with a left-handed double-helical structure. In particular, the sign at around 295 nm in CD spectra is positive for B-DNA, which is opposite to that of Z-DNA. However, it is difficult to determine the helical structure from the UV absorption spectra. Three important factors that affect the CD spectra of DNA are (1) the conformation of dG monomer, (2) the hydrogen-bonding interaction between two helices, and (3) the stacking interaction between nucleic acid bases. We calculated the CD spectra of (1) the dG monomer at different conformations, (2) the composite of dG and dC monomers, (3) two dimer models that simulate separately the hydrogen-bonding interaction and the stacking interaction, and (4) the tetramer model that includes both hydrogen-bonding and stacking interactions simultaneously. The helical structure of DNA can be clarified by a comparison of the experimental and SAC-CI theoretical CD spectra of DNA and that the sign at around 295 nm of the CD spectra of Z-DNA reflects from the strong stacking interaction characteristic of its helical structure.

Excited states of GFP chromophore and active site studied by the SAC-CI method: effect of protein-environment and mutations.

Excited states of fluorescent proteins were studied using symmetry-adapted cluster-configuration interaction (SAC-CI) method. Protein-environmental effect on the excitation and fluorescence energies was investigated. In green fluorescent protein (GFP), the overall protein-environmental effect on the first excitation energy is not significant. However, glutamine (Glu) 94 and arginine (Arg96) have the red-shift contribution as reported in a previous study (Laino et al., Chem Phys 2004, 298, 17). The excited states of GFP active site (GFP-W22-Ser205-Glu222-Ser65) were also calculated. Such large-scale SAC-CI calculations were performed with an improved code containing a new algorithm for the perturbation selection. The SAC-CI results indicate that a charge-transfer state locates at 4.19 eV, which could be related to the channel of the photochemistry as indicated in a previous experimental study. We also studied the excitation and fluorescence energies of blue fluorescent protein, cyan fluorescent protein, and Y66F. The SAC-CI results are very close to the experimental ones. The protonation state of blue fluorescent protein was determined. Conformation of cyan fluorescent protein indicated by the present calculation agrees to the experimentally observed structure.

Symmetry-adapted-cluster/symmetry-adapted-cluster configuration interaction methodology extended to giant molecular systems: ring molecular crystals.

The symmetry adapted cluster (SAC)/symmetry adapted cluster configuration interaction (SAC-CI) methodology for the ground, excited, ionized, and electron-attached states of molecules was extended to giant molecular systems. The size extensivity of energy and the size intensivity of excitation energy are very important for doing quantitative chemical studies of giant molecular systems and are designed to be satisfied in the present giant SAC/SAC-CI method. The first extension was made to giant molecular crystals composed of the same molecular species. The reference wave function was defined by introducing monomer-localized canonical molecular orbitals (ml-CMO's), which were obtained from the Hartree-Fock orbitals of a tetramer or a larger oligomer within the electrostatic field of the other part of the crystal. In the SAC/SAC-CI calculations, all the necessary integrals were obtained after the integral transformation with the ml-CMO's of the neighboring dimer. Only singles and doubles excitations within each neighboring dimer were considered as linked operators, and perturbation selection was done to choose only important operators. Almost all the important unlinked terms generated from the selected linked operators were included: the unlinked terms are important for keeping size extensivity and size intensivity. Some test calculations were carried out for the ring crystals of up to 10 000-mer, confirming the size extensivity and size intensivity of the calculated results and the efficiency of the giant method in comparison with the standard method available in GAUSSIAN 03. Then, the method was applied to the ring crystals of ethylene and water 50-mers, and formaldehyde 50-, 100-, and 500-mers. The potential energy curves of the ground state and the polarization and electron-transfer-type excited states were calculated for the intermonomer distances of 2.8-100 A. Several interesting behaviors were reported, showing the potentiality of the present giant SAC/SAC-CI method for molecular engineering.

Excited states of porphyrin isomers and porphycene derivatives: a SAC-CI study.

Excited states of free-base porphyrin isomers, porphycene (Pc), corrphycene (Cor), and hemiporphycene (hPc), were studied by the Symmetry-Adapted Cluster (SAC)/SAC-Configuration Interaction (CI) method. The absorption peaks of the porphyrin isomers were assigned on the basis of the SAC-CI spectra. The X, Y, X', and Y' bands of the porphyrin isomers, which have weak intensities, are identified. The differences in the Q-band absorptions among the isomers were clearly explained by the four-orbital model. In Cor and hPc, the wave function of the B-band corresponds to the mixture of the four-orbital excitations and the optically forbidden excitation of free-base porphin (P), due to the molecular symmetry lowering in the isomers. The B-band character is described by the five-orbital model in Pc and the six-orbital model in Cor and hPc. Two tetrazaporphycenes and two ring-extended (dibenzo) porphycenes were designed, and the Q-band transition moment was successfully controlled. These examples show that the control of the four-orbital energy levels is the guiding principle for pigment design in porphyrin compounds.

Electronic excitations of the green fluorescent protein chromophore in its protonation states: SAC/SAC-CI study.

Two ground-state protonation forms causing different absorption peaks of the green fluorescent protein chromophore were investigated by the quantum mechanical SAC/SAC-CI method with regard to the excitation energy, fluorescence energy, and ground-state stability. The environmental effect was taken into account by a continuum spherical cavity model. The first excited state, HOMO-LUMO excitation, has the largest transition moment and thus is thought to be the source of the absorption. The neutral and anionic forms were assigned to the protonation states for the experimental A- and B-forms, respectively. The present results support the previous experimental observations.