<p>The thesis contains two directions in the simulations of biomolecular systems. The first part (Chapter 2 - Chapter 4) mainly focuses on the simulations of electron transfer processes in condensed phase; the second part (Chapter 5 - Chapter 6) investigates the conformational sampling of polysaccharides and proteins. Electron transfer (ET) reaction is one of the most fundamental processes in chemistry and biology. Because of the quantum nature of the processes and the complicated roles of the solvent, calculating the accurate kinetic and dynamic properties of ET reactions is challenging but extremely useful. Based on the Marcus theory for thermal ET in weak coupling limit, we combined the rigorous ab initio quantum mechanical (QM) method and well-established molecular mechanical (MM) force field and developed an approach to directly calculate a key factor that affects the ET kinetics: the redox free energy. A novel reaction order parameter fractional number of electrons (FNE) was used to characterize the ET progress and to drive the QM/MMMD sampling of the nonadiabatic free energy surface. This method was used for two aqueous metal cations, iron and ruthenium in solution, and generated satisfactory results compared to experiments. In order to further reduce the computational cost, a QM/MM-minimum free energy path (MFEP) method is implemented and combined with the FNE in the calculation of redox free energies. The calculation results using QM/MM-MFEP+FNE generated identical results as the direct QM/MM-MD method for the two metal cations, demonstrating the consistency of the two different sampling strategy. Furthermore, this new method was applied to the calculation of organic molecules and enhanced the computational efficiency 15-30 times than the direct QM/MM-MD method, while maintaining high accuracy. Finally, I successfully extended the QM/MM-MFEP+FNE method to a series of redox proteins, azurin and its mutants, and obtained very accurate redox free energy differences with relative error less than 0.1 eV. The new method demonstrated its excellent transferability, reliability and accuracy among various conditions from aqueous solutions to complex protein systems. Therefore, it shows great promises for applications of the studies on redox reactions in biochemistry. In the studies of force-induced conformational transitions of biomolecules, the large time-scale difference from experiments presents the challenge of obtaining convergent sampling for molecular dynamics simulations. To circumvent this fundamental problem, an approach combining the replica-exchange method and umbrella sampling (REM-US) is developed to simulate mechanical stretching of biomolecules under equilibrium conditions. Equilibrium properties of conformational transitions can be obtained directly from simulations without further assumptions. To test the performance, we carried out REM-US simulations of atomic force microscope (AFM) stretching and relaxing measurements on the polysaccharide pustulan, a (1&rarr;6)-&beta;-D-glucan, which undergoes well-characterized rotameric transitions in the backbone bonds. With significantly enhanced sampling convergence and efficiency, the REMUS approach closely reproduced the equilibrium force-extension curves measured in AFM experiments. Consistent with the reversibility in the AFM measurements, the new approach generated identical force-extension curves in both stretching and relaxing simulations, an outcome not reported in previous studies, proving that equilibrium conditions were achieved in the simulations. In addition, simulations of nine different polysaccharides were performed and the conformational transitions were reexamined using the REM-US approach. The new approach demonstrated consistent and reliable performance among various systems. With fully converged samplings and minimized statistical errors, both the agreement and the deviations between the simulation results and the AFM data were clearly presented. REM-US may provide a robust approach to modeling of mechanical stretching on polysaccharides and even nucleic acids. However, the performance of the REM-US in protein systems, especially with explicit solvent model, is limited by the large system size and the complex interactions. Therefore, a Go-like model is employed to simulate the protein folding/unfolding processes controlled by AFM. The simulations exquisitely reproduced the experimental unfolding and refolding force extension relationships and led to the full reconstruction of the vectorial folding pathway of a large polypeptide, the 253-residue consensus ankyrin repeat protein, NI6C. The trajectories obtained in the simulation captured the critical conformational transitions and the rate-limiting nucleation event. Together with the AFM experiments, the coarse-grained simulations revealed the protein folding and unfolding pathways under the mechanical tension.</p> / Dissertation

No description available.

Naphthenic acids (NA) are a highly complex mixture of aliphatic carboxylic acids that may contain multiple rings and unsaturated double bonds, and are a subset of the naphthenic acid fraction components (NAFC), which can contain heteroatoms, unsaturations, and aromatic structures. Mono-carboxylated NAs can be classically represented by CnH2n+zO2 where z is a negative integer representing the hydrogen deficiency. NAs and NAFCs are components of the acid extractable organics (AEO) frequently associated with increased toxicity and observed at elevated concentrations in oil sands process waters (OSPW). Numerous chromatographic and mass spectrometry techniques have recently emerged to probe the composition and concentrations of these components. This thesis reports the use of a capillary hollow fiber polydimethylsiloxane (PDMS) membrane mounted on a probe interface that can be immersed directly into an aqueous sample. A methanol acceptor phase passing through the lumen transports analyte to an electrospray ionization source and a triple quadrupole mass spectrometer. This technique, termed condensed phase membrane introduction mass spectrometry (CP-MIMS), allows for rapid screening of m/z profiles and on-line quantification of NAs in complex samples within minutes. This thesis reports parametric studies of several model carboxylic acids and a standard naphthenic acid mixture (Merichem) involving the effect of sample pH on membrane transport and acceptor phase pH on ionization enhancement. Several quantitative strategies are explored including the use of an internal standard in the acceptor phase to correct for ionization suppression and variations in instrument sensitivity, and the use of selected ion monitoring (SIM) experiments to increase analytical sensitivity and potentially target specific NA isomer classes for quantitation. Analytical performance measures such as the linear dynamic range (1-2300 ppb [NA]T as Merichem), sensitivity (~1 ppb [NA]T as Merichem detection limit), precision (~20 %RSD for replicates of a single OSPW) and accuracy are reported. Quantitative results for various OSPW samples in the ppb to ppm range are reported as equivalents of several surrogates, including 1-pyrenebutyric acid (PyBA), Merichem, and a large-volume extract of northern Alberta OSPWs. The variety of quantitation strategies allows results to be compared with several other published methods. CP-MIMS results for three mid-range northern Alberta OSPWs are compared to analysis by Environment Canada with an average -21% bias. Results for five archived OSPWs spanning a wider concentration are compared to data from AXYS Analytical, with an average -49% bias. Applications of CP-MIMS as an in-situ monitor of removal efficiencies of NAs on adsorbents and real-time mass profile changes are also presented, along with some interpretation of the resulting high-resolution kinetic data to obtain decay constants. Using the targeted SIM method, adsorption decay can be followed in real-time for various isomer classes within the Merichem mixture, and kinetic data extracted to obtain decay constants for each. CP-MIMS is also used to characterize adsorption behavior for two activated biochars, including % removals for various loadings of each when added to stirred Merichem solutions. Preliminary multi-loading experiments are conducted with one biochar, and the ability of CP-MIMS to characterize adsorbent behavior by constructing adsorption isotherm plots is demonstrated. / Graduate

京都大学 / 新制・課程博士 / 博士(理学) / 甲第23030号 / 理博第4707号 / 新制||理||1675(附属図書館) / 京都大学大学院理学研究科化学専攻 / (主査)教授 谷村 吉隆, 教授 渡邊 一也, 教授 林 重彦 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DGAM

No description available.

The vibrational wave-packet dynamics of diatomic rubidium molecules (Rb2) in triplet states formed on the surface of superfluid helium nanodroplets is investigated both experimentally and theoretically. Detailed comparison of experimental femtosecond pump–probe spectra with dissipative quantum dynamics simulations reveals that vibrational relaxation is the main source of dephasing. The rate constant for vibrational relaxation in the first excited triplet state 13Σ+g is found to be constant γ ≈ 0.5 ns−1 for the lowest vibrational levels v [less, similar] 15 and to increase sharply when exciting to higher energies. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Ce travail est destiné au développement de méthodes approchées de chimie quantique capables de traiter des systèmes biologiques de grande taille. En particulier, nous réalisons des simulations de dynamique moléculaire dans l'approximation de Born-Oppenheimer, permettant une description quantique de l'Hamiltonien électronique du système dans son entier : SEBOMD (SemiEmpirical Born-Oppenheimer Molecular Dynamics). Notre approche se base sur un Hamiltonien électronique semiempirique (SE). L'une des principales difficultés rencontrées lors d'une simulation SEBOMD de la phase condensée est représentée par le choix de la méthode SE. La plupart des méthodes courantes ne permettant pas une bonne description de certaines interactions fondamentales, nous avons développé une nouvelle approche. Cette méthode, dénommée PM3-PIF3, a été appliquée à l'étude par dynamique moléculaire de molécules organiques dans l'eau. Les résultats obtenus montrent que notre méthode est appropriée pour le traitement de molécules comportant des groupements hydrophobes et/ou hydrophiles en milieu aqueux. L'analyse des propriétés électroniques et vibrationnelles de ces molécules en présence du solvant valide également nos résultats vis-À-Vis d'autres études expérimentales et théoriques présentes dans la littérature. Finalement, nous nous sommes intéressés au processus d'autoprotolyse de l'eau en milieux confinés. Après avoir discuté du choix de l'Hamiltonien SE à utiliser pour cette étude, nous avons caractérisé le transfert de proton dans un agrégat d'eau. Nous avons établi une corrélation entre l'énergie libre associée à la première étape de ce transfert et certaines propriétés physiques collectives / The present work is devoted to the development of approximate quantum chemistry methods that are suitable to treat biological systems of large size. In particular, we run molecular dynamics under the Born-Oppenheimer approximation, allowing a quantum mechanical description of the electronic Hamiltonian of the full system: SEBOMD (SemiEmpirical Born-Oppenheimer Molecular Dynamics). Our method is based on a semiempirical (SE) electronic Hamiltonian. One of the key issues arising in a condensed phase SEBOMD simulation is represented by the choice of the SE method. Since most of the currently available approaches fail in describing some relevant intermolecular interactions, we developed a new correction of SE Hamiltonians. This method, which we named PM3-PIF3, was applied to study the molecular dynamics of organic molecules in water. The results that we obtained showed that our technique is suitable to treat molecules having hydrophobic and/or hydrophilic groups in an aqueous medium. The analysis of the electronic and vibrational properties of these molecules in the presence of the solvent validates our results with respect to experimental and theoretical studies in the literature. Finally, we investigated the water self-Dissociation process in confined environments. After discussing the choice of the SE Hamiltonian to be used for this purpose, we characterized the proton transfer in a water cluster. We established a correlation between the free energy of the first step of this process and some collective physical properties

No description available.

"Review of the literature shows that the reported correlation between predictions and experimental data of flame spread vary greatly. The discrepancies displayed by the models are generally attributed to inaccurate input parameters, user effects, and inadequacy of the model. In most experiments, the metric to which the model is deemed accurate is based on the prediction of the heat release rate, but flame spread is a highly complex phenomenon that should not be simplified as such. Moreover, fire growth models are usually made up of distinctive groups of calculation on separate physical phenomena to predict processes that drive fire growth. Inaccuracies of any of these “sub-models” will impact the overall flame spread prediction, hence identifying the sources of error and sensitivity of the subroutines may aid in the development of more accurate models. Combating this issue required that the phenomenon of flame spread be decomposed into four components to be studied separately: turbulent fluid dynamics, flame temperature, flame heat transfer, and condensed phase pyrolysis. Under this framework, aspects of a CFD model may be validated individually and cohesively. However, a lack of comprehensive datasets in the literature hampered this process. Hence, three progressively more complex sets of experiments, from free plume fires to fires against an inert wall to combustible wall fires, were conducted in order to obtain a variety of measurements related to the four inter-related components of flame spread. Multiple permutations of the tests using different source fuels, burner size, and source fire heat release rate allowed a large amount of comparable data to be collected for validation of different fire configurations. FDS simulations using mostly default parameters were executed and compared against the experimental data, but found to be inaccurate. Parametric study of the FDS software shows that there are little definitive trends in the correlation between changes in the predicted quantities and the modeling parameters. This highlights the intricate relationships shared between the subroutines utilized by FDS for calculations related to the four components of flame spread. This reveals a need to examine the underlying calculation methods and source code utilized in FDS."

The vibrational wave-packet dynamics of diatomic rubidium molecules (Rb2) in triplet states formed on the surface of superfluid helium nanodroplets is investigated both experimentally and theoretically. Detailed comparison of experimental femtosecond pump–probe spectra with dissipative quantum dynamics simulations reveals that vibrational relaxation is the main source of dephasing. The rate constant for vibrational relaxation in the first excited triplet state 13Σ+g is found to be constant γ ≈ 0.5 ns−1 for the lowest vibrational levels v [less, similar] 15 and to increase sharply when exciting to higher energies. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.