Toshiko Ichiye

Configurational entropy of native proteins

Simulations of the residual configurational entropy of a protein in the native state suggest that it is nearly an order of magnitude larger than the entropy of denaturation. The implications of this result are discussed.

Soft sticky dipole-quadrupole-octupole potential energy function for liquid water: an approximate moment expansion.

A new, efficient potential energy function for liquid water is presented here. The new model, which is referred here as the soft sticky dipole-quadrupole-octupole (SSDQO) model, describes a water molecule as a Lennard-Jones sphere with point dipole, quadrupole, and octupole moments. It is a single-point model and resembles the hard-sphere sticky dipole potential model for water by Bratko et al. [J. Chem. Phys. 83, 6367 (1985)] and the soft sticky dipole model by Ichiye and Liu [J. Phys. Chem. 100, 2723 (1996)] except now the sticky potential consists of an approximate moment expansion for the dimer interaction potential, which is much faster than the true moment expansion. The object here is to demonstrate that the SSDQO potential energy function can accurately mimic the potential energy function of a multipoint model using the moments of that model. First, the SSDQO potential energy function using the dipole, quadruple, and octupole moments from SPC/E, TIP3P, or TIP5P is shown to reproduce the dimer potential energy functions of the respective multipoint model. In addition, in Monte Carlo simulations of the pure liquid at room temperature, SSDQO reproduces radial distribution functions of the respective model. However, the Monte Carlo simulations using the SSDQO model are about three times faster than those using the three-point models and the long-range interactions decay faster for SSDQO (1/r(3) and faster) than for multipoint models (1/r). Moreover, the contribution of each moment to the energetics and other properties can be determined. Overall, the simplicity, efficiency, and accuracy of the SSDQO potential energy function make it potentially very useful for studies of aqueous solvation by computer simulations.

DYNAMICAL PROPERTIES OF THE SOFT STICKY DIPOLE MODEL OF WATER : MOLECULAR DYNAMICS SIMULATIONS

Dynamical properties of the soft sticky dipole (SSD) model of water are calculated by means of molecular dynamics simulations. Since this is not a simple point model, the forces and torques arising from the SSD potential are derived here. Simulations are carried out in the microcanonical ensemble employing the Ewald method for the electrostatic interactions. Various time correlation functions and dynamical quantities associated with the translational and rotational motion of water molecules are evaluated and compared with those of two other commonly used models of liquid water, namely the transferable intermolecular potential-three points (TIP3P) and simple point charge/extended (SPC/E) models, and also with experiments. The dynamical properties of the SSD water model are found to be in good agreement with the experimental results and appear to be better than the TIP3P and SPC/E models in most cases, as has been previously shown for its thermodynamic, structural, and dielectric properties. Also, molecular dynamics simulations of the SSD model are found to run much faster than TIP3P, SPC/E, and other multisite models.

Dynamical properties of the soft sticky dipole-quadrupole-octupole water model: A molecular dynamics study

The dynamical properties of the soft sticky dipole-quadrupole-octupole (SSDQO) water model using SPC/E moments are calculated utilizing molecular dynamics simulations. This new potential for liquid water describes the water-water interactions by a Lennard-Jones term and a sticky potential, which is an approximate moment expansion with point dipole, quadrupole, and octupole moments, and reproduces radial distribution functions of pure liquid water using the moments of SPC/E [Ichiye and Tan, J. Chem. Phys. 124, 134504 (2006)]. The forces and torques of SSDQO water for the dipole-quadrupole, quadrupole-quadrupole, and dipole-octupole interactions are derived here. The simulations are carried out at 298 K in the microcanonical ensemble employing the Ewald method for the long-range dipole-dipole interactions. Here, various dynamical properties associated with translational and rotational motions of SSDQO water using the moments of SPC/E (SSDQO:SPC/E) water are compared with the results from SPC/E and also experiment. The self-diffusion coefficient of SSDQO:SPC/E water is found to be in excellent agreement with both SPC/E and experiment whereas the single particle orientational relaxation time for dipole vector is better than SPC/E water but it is somewhat smaller than experiment. The dielectric constant of SSDQO:SPC/E is essentially identical to SPC/E, and both are slightly lower than experiment. Also, molecular dynamics simulations of the SSDQO water model are found to be about twice as fast as three-site models such as SPC/E.

Integral equation theory of ionic solutions

A new closure to the Ornstein–Zernike equation is proposed for ionic liquids such as electrolytes. The closure is investigated numerically for a model electrolyte consisting of charged soft spheres in a uniform dielectric medium. The new closure, which we call the ionic Percus–Yevick (IPY) closure, may be viewed as a prescription for the so‐called ‘‘bridge function,’’ which is approximated by zero in the well‐known hypernetted‐chain (HNC) closure. Compared to the results of Monte Carlo simulations, the pair correlation functions predicted from this new closure for 2:2 electrolytes at low concentrations are in much better agreement than those predicted by the HNC closure. In particular, whereas the HNC approximation predicts incorrectly a peak in the pair correlation functions for like charges at an interionic separation of about two diameters at low concentrations, the new IPY closure predicts correctly no such peak. At higher concentrations, both the HNC and IPY closures yield correlation functions which...

Leucine 41 is a gate for water entry in the reduction of Clostridium pasteurianum rubredoxin

Biological electron transfer is an efficient process even though the distances between the redox moieties are often quite large. It is therefore of great interest to gain an understanding of the physical basis of the rates and driving forces of these reactions. The structural relaxation of the protein that occurs upon change in redox state gives rise to the reorganizational energy, which is important in the rates and the driving forces of the proteins involved. To determine the structural relaxation in a redox protein, we have developed methods to hold a redox protein in its final oxidation state during crystallization while maintaining the same pH and salt conditions of the crystallization of the protein in its initial oxidation state. Based on 1.5 Å resolution crystal structures and molecular dynamics simulations of oxidized and reduced rubredoxins (Rd) from Clostridium pasteurianum (Cp), the structural rearrangements upon reduction suggest specific mechanisms by which electron transfer reactions of rubredoxin should be facilitated. First, expansion of the [Fe—S] cluster and concomitant contraction of the NH • • • S hydrogen bonds lead to greater electrostatic stabilization of the extra negative charge. Second, a gating mechanism caused by the conformational change of Leucine 41, a nonpolar side chain, allows transient penetration of water molecules, which greatly increases the polarity of the redox site environment and also provides a source of protons. Our method of producing crystals of Cp Rd from a reducing solution leads to a distribution of water molecules not observed in the crystal structure of the reduced Rd from Pyrococcus furiosus. How general this correlation is among redox proteins must be determined in future work. The combination of our high‐resolution crystal structures and molecular dynamics simulations provides a molecular picture of the structural rearrangement that occurs upon reduction in Cp rubredoxin.

On the electronic structures of gaseous transition metal halide complexes, FeX4− and MX3− (M=Mn, Fe, Co, Ni, X=Cl, Br), using photoelectron spectroscopy and density functional calculations

We report a photoelectron spectroscopy (PES) and theoretical study on a series of transition metal halide complexes: FeX4− and MX3− (M=Mn, Fe, Co, Ni, X=Cl, Br). PES spectra were obtained at two photon energies (193 and 157 nm), revealing the complicated electronic structures of these metal complexes and their variation with the ligand-field geometry and metal center substitution. Density functional calculations were carried out to obtain information about the structures, energetics, and molecular orbitals of the metal complexes and used to interpret the PES spectra. For the tetrahedrally coordinated ferric complexes (FeX4−), the PES data directly confirm the “inverted level scheme” electronic structure, where the Fe 3d electrons lie below those of the ligands due to a strong spin-polarization of the Fe 3d levels. For the three-coordinate complexes (MX3−), the calculations also revealed strong spin polarizations, but the molecular orbital diagrams present a “mixed level scheme,” in which the ligand orbita...

Charge location on gas phase peptides

Studying biological systems to determine structure has been performed by a number of analytical techniques, including electrospray ionization (ESI)/ion mobility spectrometry (IMS) with mass spectrometry (MS) detection. ESI/IMS/MS enables the determination of gas phase ionic molecular size and can be correlated to computational modeling for structural evaluation. In this study, a molecular modeling program (CHARMm) coupled with a novel method of experimentally determining ion radii with ambient pressure IMS/MS was utilized to determine the charge position on gas phase peptides. Molecular modeling predicted the relative sizes of several isomeric peptides previously separated by IMS in a nitrogen buffer gas, although the modeled radii were smaller than the experimental radii due to the large polarizability of the drift gas. To correct for the polarization of the ambient pressure gas through which the ions migrate in the ion mobility experiment, ionic radii in drift gases of differing polarizability were plotted as a function of drift gas polarizability. To compare with the zero-polarizability ionic radii (y-intercept of the linear regression), the modeling experiment mimicked conditions of the actual experiment and the modeled and measured ionic size matched well. Moreover, when all possible charge locations on the peptides were modeled, only one modeled structure matched the experimental data, indicating that the combination of modeled and mobility data can determine charge location on gas phase peptides. (Int J Mass Spectrom 219 (2002) 23–37)

Insight into environmental effects on bonding and redox properties of [4Fe-4S] clusters in proteins.

The large differences in redox potentials between the HiPIPs and ferredoxins are generally attributed to hydrogen bonds and electrostatic effects from the protein and solvent. Recent ligand K-edge X-ray absorption studies by Solomon and co-workers show that the Fe-S covalencies of [4Fe-4S] clusters in the two proteins differ considerably apparently because of hydrogen bonds from water, indicating electronic effects may be important. However, combined density function theory (DFT) and photoelectron spectroscopy studies by our group and Wang and co-workers indicate that hydrogen bonds tune the potential of [4Fe-4S] clusters by mainly electrostatics. The DFT studies here rationalize both results, namely that the observed change in the Fe-S covalency is due to differences in ligand conformation between the two proteins rather than hydrogen bonds. Moreover, the ligand conformation affects the calculated potentials by approximately 100 mV and, thus, is a heretofore unconsidered means of tuning the potential.

A temperature of maximum density in soft sticky dipole water

A temperature of maximum density near 260 K at 1 atm has been found for the soft sticky dipole (SSD) water model in molecular dynamics simulations. The parameters of SSD have been optimized to reproduce the density of water as well as other structural, thermodynamic, dielectric, and dynamic properties at room temperature and 1 atm. Remarkably, this simple model is able to reproduce the anomalous temperature dependence of the density using parameters optimized at room temperature. Furthermore, these results indicate that the tetrahedral nature of water is important in determining this anomalous behavior.