Hochan Lee

Correlation between electronic and molecular structure distortions and vibrational properties. II. Amide I modes of NMA–nD2O complexes

Hydration effects on the molecular structure and amide I mode frequency of a prototype peptide molecule, N-methylacetamide (NMA), when it is solvated by a few water molecules, were investigated by carrying out ab initio calculations for a number of NMA–water complexes. The harmonic frequency shift of the amide I mode in NMA–nD2O (n=1–5) complex was found to originate from the combination of the molecular cubic anharmonicity and displacement of the amide I coordinate when the NMA is hydrated. Using a multivariate least-square fitting method, the effective transition charges of six NMA sites were determined. A brief discussion on how this empirical model can be used to quantitatively describe solvatochromic frequency shift of the NMA amide I mode in solution is presented.

Nitrile and thiocyanate IR probes: Quantum chemistry calculation studies and multivariate least-square fitting analysis

Hydration effects on the C[Triple Bond]N stretching mode frequencies of MeCN and MeSCN are investigated by carrying out ab initio calculations for a number of MeCN-water and MeSCN-water complexes with varying number of water molecules. It is found that the CN frequency shift induced by the hydrogen-bonding interactions with water molecules originate from two different ways to form hydrogen bonds with the nitrogen atom of the CN group. Considering the MeCN- and MeSCN-water cluster calculation results as databases, we first examined the validity of vibrational Stark effect relationship between the CN frequency and the electric field component parallel to the CN bond and found no strong correlation between the two. However, taking into account of additional electric field vector components is a simple way to generalize the vibrational Stark theory for the nitrile chromophore. Also, the electrostatic potential calculation method has been proposed and examined in detail. It turned out that the interactions of water molecules with nitrogen atoms lone pair orbital and with nitrile pi orbitals can be well described by the electrostatic potential calculation method. The present computational results will be of use to quantitatively simulate various linear and nonlinear vibrational spectra of nitrile compounds in solutions.

Non-Gaussian statistics of amide I mode frequency fluctuation of N-methylacetamide in methanol solution: Linear and nonlinear vibrational spectra

By carrying out molecular dynamics simulations of an N-methylacetamide (NMA) in methanol solution, the amide I mode frequency fluctuation and hydrogen bonding dynamics were theoretically investigated. Combining an extrapolation formula developed from systematic ab initio calculation studies of NMA-(CH3OH)n clusters with a classical molecular dynamics simulation method, we were able to quantitatively describe the solvatochromic vibrational frequency shift induced by the hydrogen-bonding interaction between NMA and solvent methanol. It was found that the fluctuating amide I mode frequency distribution is notably non-Gaussian and it can be decomposed into two Gaussian peaks that are associated with two distinctively different solvation structures. The ensemble-average-calculated linear response function associated with the IR absorption is found to be oscillating, which is in turn related to the doublet amide I band shape. Numerically calculated infrared absorption spectra are directly compared with experiment and the agreement was found to be excellent. By using the Onsagers regression hypothesis, the rate constants of the interconversion process between the two solvation structures were obtained. Then, the nonlinear response functions associated with two-dimensional infrared pump-probe spectroscopy were simulated. The physics behind the two-dimensional line shape and origin of the cross peaks in the time-resolved pump-probe spectra is explained and the result is compared with 2D spectra experimentally measured recently by Woutersen et al.

Nitrile and thiocyanate IR probes: Molecular dynamics simulation studies

Nitrile- and thiocyanate-derivatized amino acids have been found to be useful IR probes for investigating their local electrostatic environments in proteins. To shed light on the CN stretch frequency shift and spectral lineshape change induced by interactions with hydrogen-bonding solvent molecules, we carried out both classical and quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) simulations for MeCN and MeSCN in water. These QM/MM and conventional force field MD simulation results were found to be inconsistent with the experimental results as well as with the high-level ab initio calculation results of MeCN-water and MeSCN-water potential energies. Thus, a new set of atomic partial charges of MeCN and MeSCN is obtained. By using the MD simulation trajectories and the electrostatic potential model recently developed, the CN and SCN stretching mode frequency trajectories were obtained and used to simulate the IR spectra. The C[Triple Bond]N frequency blueshifts of MeCN and MeSCN in water are estimated to be 9.0 and 1.9 cm(-1), respectively, in comparison with those of gas phase values. These values are found to be in reasonable agreement with the experimentally measured IR spectra of MeCN, MeSCN, beta-cyano-L-alanine, and cyanylated cysteine in water and other polar solvents.

Computational spectroscopy of ubiquitin: comparison between theory and experiments.

Using the constrained molecular dynamics simulation method in combination with quantum chemistry calculation, Hessian matrix reconstruction, and fragmentation approximation methods, the authors have established computational schemes for numerical simulations of amide I IR absorption, vibrational circular dichroism (VCD), and two-dimensional (2D) IR photon echo spectra of the protein ubiquitin in water. Vibrational characteristic features of these spectra in the amide I vibration region are discussed. From the semiempirical quantum chemistry calculation results on an isolated ubiquitin, amide I local mode frequencies and vibrational coupling constants were fully determined. It turns out that the amide I local mode frequencies of ubiquitin in both gas phase and aqueous solution are highly heterogeneous and site dependent. To directly test the quantitative validity of thus obtained spectroscopic properties, they compared the experimentally measured amide I IR, 2D IR, and electronic circular dichroism spectra with experiments, and found good agreements between theory and experiments. However, the simulated VCD spectrum is just qualitatively similar to the experimentally measured one. This indicates that, due to delicate cancellations between the positive and negative VCD contributions, the prediction of protein VCD spectrum is critically relied on quantitative accuracy of the theoretical model for predicting amide I local mode frequencies. On the basis of the present comparative investigations, they found that the site dependency of amide I local mode frequency, i.e., diagonal heterogeneity of the vibrational Hamiltonian matrix in the amide I local mode basis, is important. It is believed that the present computational methods for simulating various vibrational and electronic spectra of proteins will be of use in further refining classical force fields and in addressing the structure-spectra relationships of proteins in solution.

Vibrational solvatochromism and electrochromism of cyanide, thiocyanate, and azide anions in water

Small IR probe molecules have been found to be useful to measure local electric fields in condensed phases and proteins and also to study nucleic acid and protein structure and dynamics by monitoring their vibrational couplings and frequency shifts. However, it is still difficult to accurately describe the vibrational solvatochromic frequency shifts of such IR probes, because the local electric fields produced by surrounding solvent molecules or by protein peptide and side groups are spatially non-uniform and highly inhomogeneous around a probe. We recently developed a distributed interaction site model to describe the vibrational solvatochromism and electrochromism of nitrile-, thiocyanato-, and azido-derivatized compounds and amino acids in solutions. Here, the nitrile or azido stretch is the maker mode. It was found that those interaction sites distributed over the IR probe molecule collectively act as an antenna sensing local electric field distributions around the IR probes. Once the vibrational solvatochromism of a given IR probe is understood, it becomes possible to quantitatively describe their vibrational Stark effects. Carrying out quantum chemistry calculations of cyanide, thiocyanate, and azide anions in water clusters, we extended the distributed site model for ionic IR probes and calculated the vibrational Stark tuning rates for direct comparisons with experimental results. It turns out that the charge transfers from an anionic solute to surrounding water molecules are significant, but their effects on vibrational solvatochromism and electrochromism of pseudohalide ionic IR probes are not. We anticipate that the present computational results will be of use to establish the relationship between vibrational frequency of an ionic IR probe and local electric field in condensed phases and protein matrices.

G protein β3 subunit, interleukin‐10, and tumor necrosis factor‐α gene polymorphisms in Koreans with irritable bowel syndrome

Background  The association between irritable bowel syndrome (IBS) based on Rome III criteria and G protein β3 subunit (GNB3), interleukin (IL)‐10, and tumor necrosis factor (TNF)‐α gene polymorphisms is uncertain.

Theoretical calculations of infrared absorption, vibrational circular dichroism, and two-dimensional vibrational spectra of acetylproline in liquids water and chloroform.

Infrared absorption, vibrational circular dichroism, and two-dimensional infrared pump-probe and photon echo spectra of acetylproline solutions are theoretically calculated and directly compared with experiments. In order to quantitatively determine interpeptide interaction-induced amide I mode frequency shifts, high-level quantum chemistry calculations were performed. The solvatochromic amide I mode frequency shift and fluctuation were taken into account by carrying out molecular dynamics simulations of acetylproline dissolved in liquids water and chloroform and by using the extrapolation method developed recently. We first studied correlation time scales of the two amide I vibrational frequency fluctuations, cross correlation between the two fluctuating local mode frequencies, ensemble averaged conformations of the acetylproline molecule in liquids water and chloroform. The corresponding conformations of the acetylproline in liquids water and chloroform are close to the ideal 3(10) helix and the C(7) structure, respectively. A few methods proposed to determine the angle between the two transition dipoles associated with the amide I vibrations were tested and their limitations are discussed.

Nonlinear optical properties of tetrahedral donor–acceptor octupolar molecules: Effective five-state model approach

Theoretical descriptions of the molecular nonlinear optical properties of tetrahedral donor–acceptor molecules are presented by using a valence-bond and four charge-transfer state model. Based on this five-state model, as the extent of the charge transfer from the peripheral donors (acceptors) to the central acceptor (donor) increases, the first hyperpolarizability monotonically increases. The theoretical predictions are confirmed by carrying out ab initio calculations of the first hyperpolarizabilities of three different series of tetrahedral molecules. The π-electron delocalization effect on the nonlinear optical property is elucidated by making a comparison of the first hyperpolarizability of the tetrahedral molecule with that of fictitious tetrahedrally assembled linear polyynes.

Vibrational solvatochromism and electrochromism. II. Multipole analysis

Small infrared probe molecules have been widely used to study local electrostatic environment in solutions and proteins. Using a variety of time- and frequency-resolved vibrational spectroscopic methods, one can accurately measure the solvation-induced vibrational frequency shifts and the timescales and amplitudes of frequency fluctuations of such IR probes. Since the corresponding frequency shifts are directly related to the local electric field and its spatial derivatives of the surrounding solvent molecules or amino acids in proteins, one can extract information on local electric field around an IR probe directly from the vibrational spectroscopic results. Here, we show that, carrying out a multipole analysis of the solvatochromic frequency shift, the solvatochromic dipole contribution to the frequency shift is not always the dominant factor. In the cases of the nitrile-, thiocyanato-, and azido-derivatized molecules, the solvatochromic quadrupole contributions to the corresponding stretch mode frequency shifts are particularly large and often comparable to the solvatochromic dipole contributions. Noting that the higher multipole moment-solvent electric field interactions are short range effects in comparison to the dipole interaction, the H-bonding interaction-induced vibrational frequency shift can be caused by such short-range multipole-field interaction effects. We anticipate that the present multipole analysis method specifically developed to describe the solvatochromic vibrational frequency shifts will be useful to understand the intermolecular interaction-induced vibrational property changes and to find out a relationship between vibrational solvatochromism and electrochromism of IR probes in condensed phases.