Tomoo Miyahara

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.

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.

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.

Ground and excited states of linked and fused zinc porphyrin dimers: Symmetry adapted cluster (SAC)-configuration interaction (CI) study

The symmetry adapted cluster (SAC)/SAC-configuration interaction method was applied to calculate the ground and excited states of zinc porphyrin monomers (without and with phenyl groups, ZnP and ZnPPh, respectively) and meso–meso linked (Zn2PMM) and doubly fused (Zn2PDF) zinc porphyrin dimers. Various features of the absorption spectra are studied, clarified, and assigned theoretically. The calculated electronic spectrum of ZnPPh, in comparison with that of ZnP, showed that the phenyl groups affect the spectrum in both the peak positions and intensities. In the dimers, Zn2PMM and Zn2PDF, the interactions of the monomer’s four-orbitals result in an eight-orbital model of the dimers, which plays an important role in the interpretation of the excited states observed in the spectra. In Zn2PMM, the interaction is smaller and each peak in the split Soret (BI and BII) bands consists of two peaks, in contrast to the prediction based on Kasha’s exciton rule. In Zn2PDF, the interaction between the two monomer units...

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-CMOs), 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-CMOs 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.

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.

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.

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).

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.

Circular Dichroism Spectroscopy with the SAC-CI Methodology: A ChiraSac Study

Circular dichroism (CD) spectroscopy reflects sensitively the various chemistries involved in chiral molecules and molecular systems. The CD spectra are very sensitive to the conformational changes of molecules: the rotation around the single bond including a chiral atom. It is also sensitive to the changes in the stacking interactions in the chiral DNA and RNA. Since these changes are low-energy processes, we expect that the CD spectra include a lot of information of the chiral molecular systems. On the other hand, the SAC-CI method is a highly reliable excited-state theory and gives very reliable theoretical CD spectra. Therefore, by comparing the experimental CD spectra with the theoretical SAC-CI spectra calculated for various chemical situations, one can study various chemistries such as the nature of the weak interactions involved in chiral molecular systems and biology. Based on these facts, we are developing a new molecular technology called ChiraSac, a term combining chirality and SAC-CI, to study chiral molecular systems and the chemistry involved thereof. We utilize highly reliable SAC-CI method together with many useful quantum chemical methods involved in Gaussian suite of programs. In this chapter, we review our ChiraSac studies carried out to clarify the chemistries of some chiral molecules and molecular systems: large dependences of the CD spectra on the conformations of several chiral molecules in solutions and the effects of the stacking interactions of the nuclear-acid bases in DNA and RNA on the shapes of their CD spectra. The results of our several studies show that the ChiraSac is a useful tool for studying the detailed chemistry involved in chiral molecular and biological systems.