Kiyoshi Yagi

The amide I, II, and III spectra of the insulin dimer and ubiquitin were investigated using our recently developed localized, second-order vibrational quasi-degenerate perturbation theory (VQDPT2) combined with quantum mechanics/molecular mechanics calculations. By averaging over ten snapshots from molecular dynamics trajectories, we confirmed that the computed spectra converged to a sufficient degree. Although the method has intrinsic limitations due to the neglect of vibrational coupling between neighboring amide groups, we found that the method provides a useful basis for spectral analysis of these proteins. The analysis of the averaged amide I, II, and III bands revealed that, for both proteins, the amide II and III peak positions tend to be closely associated with the coil contribution, whereas the origin of the amide I maximum is more protein dependent. The calculated amide I and III frequencies of the coil structures showed good agreement with experimental values. The spectra of each secondary structure were further subdivided according to the type of hydrogen bonding within the secondary structure. For structurally constrained α-helix and β-sheet structures, hydrogen-bond-dependent amide I frequency shifts were found to correlate with changes in the amide dihedral angles (O=C–N–H). Localized VQDPT2 enables direct interpretation of amide band shifts associated with conformational changes and provides a deeper understanding of the structural origin responsible for these band shifts.

Molecule-specific tuning of range-separated hybrid (RSH) density functionals improves time-dependent density functional theory calculations. We show that Koopmans-compliant tuning becomes underdetermined for multi-parameter RSH functionals and introduce an MP2 density-matrix criterion to remove this degeneracy. Bayesian optimisation was applied to LCgau-BLYP and CAM-B3LYP for seven organic chromophores. Optimised LCgau-BLYP reduced the absorption-wavelength RMSE from 107.6 to 39.6 nm, while CAM-B3LYP outperformed Koopmans-only tuning. The proposed strategy provides a physically motivated route to stable molecule-specific RSH parameterisation.

We present an approach for calculating three-mode-coupling Fermi-resonance Raman spectra of acetonitrile molecules in solution by combining the Reference Interaction Site Model Self-Consistent Field method coupled with the constrained Spatial Electron Density Distribution (RISM-SCF-cSED) and second-order vibrational quasi-degenerate perturbation theory (VQDPT2). By describing solvents using integral equation theory and modeling anharmonic vibrations with VQDPT2, this method enables efficient computation of three-mode-coupling Fermi resonance Raman spectra of acetonitrile in solution at a modest computational cost. We demonstrate its application to acetonitrile in water and to acetonitrile-water mixture solutions, showing that the predicted peak positions and solvent-induced shifts in the Raman spectra agree well with experiment. Analysis of radial distribution functions indicates that the packing of water molecules around the cyano group of acetonitrile influences the nonlinear, high-frequency shift of its cyano stretching vibration in solution.

We propose a constrained Møller–Plesset second-order perturbation theory (CMP2) that incorporates electron correlation into the constrained Hartree–Fock (CHF) framework. In CMP2, the CHF solution is employed as the reference state, and a common Lagrange multiplier is introduced for both the zeroth-order and constraint Hamiltonians, enabling the inclusion of correlation effects with minimal modification to existing MP2 implementations. Two schemes are developed for determining the Lagrange multiplier: (i) CMP2-i (iterative), which iteratively updates the multiplier until the MP2 electron density satisfies the constraint, and (ii) CMP2-s (single-shot), which performs a single MP2 calculation using a CHF reference that satisfies the constraint at the Hartree–Fock level. The methods are applied to an intramolecular charge-transfer reaction of the 1,3-dinitrobenzene anion radical. CMP2-s significantly reduces computational cost while reproducing relative energy profiles comparable with CMP2-i. In addition, adiabatic energy profiles obtained with configuration interaction calculations based on CMP2 (CMP2-CI) are in good agreement with those from extended multistate complete active space second-order perturbation theory (XMS-CASPT2), demonstrating that the present approach provides a practical and efficient extension of constrained electronic structure methods to the post-Hartree–Fock level.

Vibrational quasi-degenerate perturbation theory (VQDPT2) based on localized vibrational modes is combined with quantum mechanics/molecular mechanics (QM/MM) calculations to investigate the amide bands of bovine rhodopsin in the dark (inactive) and Meta II (active) states. A novel localization scheme has been developed for this purpose: (1) the protein is partitioned into individual amide-group subsystems, (2) the vibrational spectrum of each amide group is calculated by QM/MM and VQDPT2, and (3) the total spectrum is constructed by summing the individual local amide spectra. Our approach reproduces the experimental IR difference spectrum upon photoactivation across the amide I, II, and III regions, demonstrating the importance of accounting for anharmonicity. Detailed analysis has revealed that the amide I band signals are not localized to a single domain; rather, the higher-wavenumber shifts are primarily driven by helical regions, while lower-wavenumber shifts stem from loop regions. We identified specific residues, such as Thr118 and Trp265, whose significant frequency shifts are coupled to local structural rearrangements. This subsystem-based anharmonic vibrational approach provides a powerful tool for the microscopic interpretation of vibrational spectra in large biomolecular systems.

N-[2-(Trimethylammonium)ethyl]-1,8-naphthalimide (TENI) is a promising, versatile anion sensor that can detect the electronegativity of a target anion depending on the fluorescence intensity. In TENI, an emission from a lower-energy state than the first excited state of a single TENI is observed experimentally, and its character has remained unknown. Here, we have investigated the origin of the lower-energy peaks in the fluorescence spectrum of TENI using molecular dynamics (MD) simulations and time-dependent density functional theory (TD-DFT) calculations with three functionals. The computation reveals that TENIs form a structural ensemble in solution, and that stacked TENI dimers exhibit red-shifted fluorescence compared to a single TENI. The formation of excimer results in the longer-wavelength fluorescence that can be corroborated by changes in frontier orbital energies due to the intermolecular interaction. Our work will provide valuable knowledge for the development of new anion sensors.

Vibrational quasi-degenerate perturbation theory (VQDPT2) based on localized vibrational modes is combined with quantum mechanics / molecular mechanics (QM/MM) calculations to investigate the amide bands of bovine rhodopsin in dark (inactive) and Meta II (active) states. The total vibrational spectrum is reconstructed by partitioning the protein into individual amide-group subsystems. Our approach reproduces the experimental IR difference spectrum upon photoactivation across the amide I, II, and III regions, demonstrating the importance of accounting for anharmonicity. Detailed analysis has revealed that the amide I band signals are not localized to a single domain; rather, the higher-wavenumber shifts are primarily driven by helical regions, while lower-wavenumber shifts stem from loop regions. We identified specific residues, such as Thr118 and Trp265, whose significant frequency shifts are coupled with local structural rearrangements. This subsystem-based anharmonic vibrational approach provides a powerful tool for the microscopic interpretation of vibrational spectra in large biomolecular systems.

Vibrational quasi-degenerate perturbation theory (VQDPT2) based on localized vibrational modes is combined with quantum mechanics / molecular mechanics (QM/MM) calculations to investigate the amide bands of bovine rhodopsin in dark (inactive) and Meta II (active) states. The total vibrational spectrum is reconstructed by partitioning the protein into individual amide-group subsystems. Our approach reproduces the experimental IR difference spectrum upon photoactivation across the amide I, II, and III regions, demonstrating the importance of accounting for anharmonicity. Detailed analysis has revealed that the amide I band signals are not localized to a single domain; rather, the higher-wavenumber shifts are primarily driven by helical regions, while lower-wavenumber shifts stem from loop regions. We identified specific residues, such as Thr118 and Trp265, whose significant frequency shifts are coupled with local structural rearrangements. This subsystem-based anharmonic vibrational approach provides a powerful tool for the microscopic interpretation of vibrational spectra in large biomolecular systems.

The effect of pentaerythritol (PERT) as a nucleating agent on the crystallization behavior of poly­[(R)-3-hydroxybutyrate-co-(R)-3-hydroxy­hexannoate] (P­(3HB-co-3HH)) was examined. Isothermal crystallizations with and without PERT at various temperatures were monitored in real time using simultaneous synchrotron radiation wide-angle X-ray diffraction and small-angle X-ray scattering techniques. Heterogeneous nucleation was observed at significantly higher temperatures, where the crystallization of pure P­(3HB-co-3HH) scarcely occurs. The crystal form and morphological parameters of P­(3HB) remained unchanged in the presence of the nucleating agent. However, the induction period for crystallization with PERT was significantly reduced. Structural analysis confirmed that the nucleating agent enhances overall crystallinity due to a higher density of nucleation sites. In addition, the interaction between the molecular chain and the substrate surface was investigated through molecular dynamics (MD) simulations. The MD simulations indicated that the molecular chain tends to interact attractively with the substrate surface, with the carbonyl groups of P­(3HB) oriented toward the hydroxy groups of PERT. These results suggested that the formation of hydrogen bonds, rather than crystalline lattice matching, plays a crucial role in the heterogeneous nucleation of P­(3HB) on PERT.

To elucidate the relationship between conformational changes upon protein folding and amide I bands of infrared (IR) spectrum, we investigated amide I bands of chignolin, which not only folds to a native, β-hairpin conformation but also misfolds to another conformation. Chignolin’s conformations were sampled using molecular dynamics (MD) simulations, and their spectra of amide groups were calculated using vibrational calculations with the quantum mechanical/molecular mechanical (QM/MM) method. The calculated spectrum of each microstate of chignolin reflects its conformational characteristics. Our calculations reveal how the secondary structure formation affects the contribution of each amide group to the total spectrum. We also show that the population distribution of microstates can be modified by monitoring the match between the calculated and experimental spectra, which effectively fix the bias in the initial distribution caused by the force field used. Our results suggest the existence of a misfolded state in the wild-type chignolin, although the state is not detected by NMR experiments. The calculation method proposed here is useful for interpreting the amide I band and understanding the structure-spectrum relationship.