Scientific Publications 2006
2006. "Mis-translation of a Computationally Designed Protein Yields an Exceptionally Stable Homodimer: Implications for Protein Engineering and Evolution." Journal of Molecular Biology 362(5):1004-1024. doi:10.1016/j.jmb.2006.07.092 Abstract We recently used computational protein design to create an extremely stable, globular protein, Top7, with a sequence and fold not observed previously in nature. Since Top7 was created in the absence of genetic selection, it provides a rare opportunity to investigate aspects of the cellular protein production and surveillance machinery that are subject to natural selection. Here we show that a portion of the Top7 protein corresponding to the final 49 C-terminal residues is efficiently mistranslated and accumulates at high levels in E. coli. We used circular dichroism spectroscopy, size-exclusion chromatography, small-angle x-ray scattering, analytical ultra-centrifugation, and NMR spectroscopy to show that the resulting CFr protein adopts a compact, extremely-stable, obligate, symmetric, homo-dimeric structure. Based on the solution structure, we engineered an even more stable variant of CFr by disulfide-induced covalent circularisation that should be an excellent platform for design of novel functions. The accumulation of high levels of CFr exposes the high error rate of the protein translation machinery, and the rarity of correspondingly stable fragments in natural proteins implies a stringent evolutionary pressure against protein sub-fragments that can independently fold into stable structures. The symmetric self-association between two identical mistranslated CFr sub-units to generate an extremely stable structure parallels a mechanism for natural protein-fold evolution by modular recombination of stable protein sub-structures.
2006. "Highly Oxidizing Excited States of Re and Tc Complexes." Journal of the American Chemical Society 128(51):16494-16495. doi:10.1021/ja067114g Abstract Like the Re analog, the ligand-to-metal charge transfer (LMCT) excited state of [Tc(dmpe)3]2+* (dmpe is bis-1,2-(dimethylphosphino)ethane) is luminescent in solution at room temperature. Surprisingly, both [M(dmpe)3]2+* species have extremely oxidizing excited state potentials (ESPs)-the highest for any simple coordination complex of a transition metal. Furthermore, this potential is available using a photon of visible light (calculated for M=Re(Tc); E1/2*=+2.61(2.52)V vs. SCE; λmax =526(585) nm). Using a Rehm-Weller analysis with a series of aromatic hydrocarbons as electron transfer quenchers, E1/2(Re2+*/Re+) has been determined to be 2.58 V, in good agreement with the calculated value. Both [M(dmpe)3]2+* species are quenched by chloride ion and both can function as excited state oxidants in water solution.
2006. "Cancrinite and Sodalite Formation in the Presence of Cesium, Potassium, Magnesium, Calcium and Strontium in Hanford Tank Waste Simulants." Applied Geochemistry 21(12):2049-2063. Abstract High-level radioactive tank waste solutions that have leaked into the subsurface at the US Department of Energy Hanford Site, Washington, are chemically complex. Here, the effect of five cations, Cs⁺, K⁺, Sr²⁺, Ca²⁺ and Mg²⁺, on mineral formation and transformation pathways under conditions mimicking Hanford tank leaks is investigated. Sodium silicate was used to represent the dissolved silicate from sediments. The silicate was added into a series of simulants that contained 0.5 M aluminate, 1M or 16 M NaOH, and the NO⁻₃ salts of the cations. The precipitates were monitored by X-ray diffraction, scanning electron microscopy, and X-ray energy dispersive spectroscopy. In the 1M NaOH simulants, low concentration of Cs⁺ (<100 mM) did not affect the formation of lepispheric cancrinite and sodalite, whereas only highly crystalline cancrinite formed when Cs⁺ concentration was ≥250 mM. An unidentified feldspathoid or zeolite intermediate phase was observed in the presence of high concentrations of Cs⁺ (500 mM). The presence of K⁺ did not alter, but slowed, the formation of cancrinite and sodalite. The presence of divalent cations led to the formation of metastable or stable silicates, aluminates, hydroxides, or aluminosilicates. The formation of these intermediate phases slowed the formation of cancrinite and sodalite by consuming OH⁻, silicate, or aluminate. Compared with the concentrations used in this study, the concentrations of radioactive Cs+ and Sr²⁺ in the tank solutions are much lower and divalent cations (Ca²⁺ and Mg²⁺) released from sediments likely precipitate out as hydroxides, silicates or aluminates; therefore, the authors do not expect that the presence of these monovalent and divalent cations significantly affect the formation of cancrinite and sodalite in the sediments underneath the leaking waste tanks.
2006. "Atomistic Simulation of Collision Cascades in Zircon." Nuclear Instruments and Methods in Physics Research. Section B, Beam Interactions with Materials and Atoms 250(1-2):46-49. doi:10.1016/j.nimb.2006.04.109 Abstract Defect production in energetic collision cascades in zircon has been studied by molecular dynamics simulation using a partial charge model combined with the Ziegler-Biersack-Littmark potential. Energy dissipation, defect accumulation, Si-O-Si polymerization, and Zr coordination number were examined for 10 keV and 30 keV U recoils simulated in the constant NVE ensemble. For both energies an amorphous core was produced with features similar to that of melt quenched zircon. Disordered Si ions in this core were polymerized with an average degree of polymerization of 1.5, while disordered Zr ions showed a coordination number of about 6 in agreement with EXAFS results. These results suggest that nano-scale phase separation into silica- and zirconia-rich regions occurs in the amorphous core.
2006. "Molecular Dynamics Simulation of Energetic Uranium Recoil Damage in Zircon." Molecular Simulation 32(12-13):1069-1077. Abstract Defect production and amorphisation due to energetic uranium recoils in zircon (ZrSiO4), which is a promising ceramic nuclear waste form, is studied using molecular dynamics simulations with a partial charge model. An algorithm that distinguishes between undamaged crystal, crystalline defects and amorphous regions is used to develop a fundamental understanding of the primary damage state. The amorphous cascade core is separated from the surrounding crystal by a defect-rich region. Small, chemically inhomogeneous amorphous clusters are also produced around the core. The amorphous regions consist of under-coordinated Zr and polymerised Si leading to amorphisation and phase separation on a nanometer scale into Zr- and Si-rich regions. This separation could play an important role in the experimentally observed formation of nanoscale ZrO2 in ZrSiO4 irradiated at elevated temperatures.
2006. "HepatoProteomics: Applying Proteomic Technologies to the Study of Liver Function and Disease." Hepatology 44(2):299-308. Abstract The wealth of human genome sequence information now available, coupled with technological advances in robotics, nanotechnology, mass spectrometry, and information systems, has given rise to a method of scientific inquiry known as functional genomics. By using these technologies to survey gene expression and protein production on a near global scale, the goal of functional genomics is to assign biological function to genes with currently unknown roles in physiology. This approach carries particular appeal in disease research, where it can uncover the function of previously unknown genes and molecular pathways that are directly involved in disease progression. With this knowledge may come improved diagnostic techniques, prognostic capabilities, and novel therapeutic approaches. In this regard, the continuing evolution of proteomic technologies has resulted in an increasingly greater impact of proteome studies in many areas of research and hepatology is no exception. Our laboratory has been extremely active in this area, applying both genomic and proteomic technologies to the analysis of virus-host interactions in several systems, including the study of hepatitis C virus (HCV) infection and HCV-associated liver disease. Since proteomic technologies are foreign to many hepatologists (and to almost everyone else), this article will provide an overview of proteomic methods and technologies and describe how they’re being used to study liver function and disease. We use our studies of HCV infection and HCV-associated liver disease to present an operational framework for performing high throughput proteome analysis and extracting biologically meaningful information.
2006. "The Proteome of Dissimilatory Metal-reducing Microorganism Geobacter Sulfurreducens under Various Growth Conditions." Biochimica et Biophysica Acta--Proteins and Proteomics 1764(7):1198-1206. doi:10.1016/j.bbapap.2006.04.017 Abstract The global protein analysis of Geobacter sulfurreducens, a model for the Geobacter species that predominate in many Fe(III)-reducing subsurface environments, was characterized with ultra high pressure liquid chromatography and mass spectrometry using accurate mass and time (AMT) tags as well as with more traditional two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). Cells were grown under eight different growth conditions in order to enhance the potential that genes would be expressed. Over 3,187 gene products, representing about 92% of the total predicted gene products in the genome, were detected. The AMT approach was able to identify a much higher number of proteins than could be detected with the 2-D PAGE approach. A high proportion of predicted proteins in most protein role categories were detected with the highest number of proteins identified in the hypothetical protein role category. Furthermore, 91 c-type cytochromes of 111 predicted genes in the G. sulfurreducens genome were identified. Localization studies indicated that computational predictions of cytochrome location were limited. Differences in the abundance of cytochromes and other proteins under different growth conditions provided information for future functional analysis of these proteins. These results demonstrate that a high percentage of the predicted proteins in the G. sulfurreducens genome are produced and that the AMT approach provides a rapid method for comparing differential expression of proteins under different growth conditions in this organism.
2006. "Developing Multiple-Site Kinetic Models in Catalysis Simulation: A Case Study of 02+2N0 ↔ 2 NO2 Oxidation-Reduction Chemistry on Pt(100) Catalyst Crystal Facets." Journal of Catalysis 238(1):1-5. doi:10.1016/j.jcat.2005.11.031 Abstract It is generally recognized that developing a kinetic model for a supported catalyst is difficult since multiple site types exist. These sites can arise from a distribution of crystal facets (e.g., (100), (110), etc.) each with their unique intrinsic site types (e.g., atop, bridge, hollow, etc.). Additional complexities arise from non-basel plane site types (defect, edge, corner, etc.), all whose differing lateral interaction energies may be coverage dependent for each site pairwise interaction. To demonstrate the complexities that develop even for a greatly simplified system, we examine a multiple site kinetic model of the reaction 2NO + O2 - 2NO2 on an ideal Pt(100) catalyst. A model of the Pt(100) surface is adopted where atop, bridge, and 4-fold hollow sites are responsible for O2, NO, and NO2 chemisorption to form Pt-O, Pt-NO, and Pt-NO2 species. In our kinetic scheme, equilibrium is assumed for O2, NO, and NO2 chemisorption due to their high sticking coefficients (all > 0.1). A single rate determining step of the Langmuir-Hinshelwood type was chosen to describe the oxidation of NO on platinum via the reaction PtH,A,B-O + PtH,A,B-NO - PtH,A,B + PtH,A,B-NO2, where H, A, and B represent 4-fold hollow, atop, and bridge sites. Equal kinetic parameters for all site combinations were assumed to exist and, in part, taken from the literature to be AH+=83 kJ/mol and AS+=20 J/K mol. The exercise here is largely hypothetical but offers insight into how more detailed kinetic models may be developed, such as through the use of reaction velocity matrices, a concept introduced here. Specifically for this system, the model yielded insight into NOx chemistry on Pt(100) in that it predicted that the greatest reaction velocities (forward and reverse) occurred via the reaction Pt-O(atop) + Pt-NO(bridge) A Pt(atop) + Pt-NO2(bridge). We believe the framework of a site-specific modeling scheme presented here is an important starting point for future site-specific microkinetic modeling. In particular, a definition and description of use of surface coverages, reaction rate coefficients, and computed reaction velocity matrices are presented.
2006. "Non-equilibrium Effects in the Hydrogenation-mediated Isomerization Mechanism of Olefins during Cavitating Ultrasound Processing." Catalysis Communications 7(6):348–350. doi:10.1016/j.catcom.2005.10.021 Abstract The process whereby cis-olefins isomerize to their trans form is generally understood as occurring through C-H activation of surface bound alkyl radical species. Here we present aqueous phase deuteration results of cis-2-buten-1-ol on Raney Nickel. In the context of the accepted olefin isomerization mechanism, our results illustrate that transition-state theory can accurately model the competition between C-H and C-D activation for olefin exchange (isomerization) for the case of conventional catalytic processing. This is the case also for a catalytic process that includes cavitating ultrasound, although the model then requires a much higher vibrational temperature (at least ~800 K) in order to simulate the selectivity of the deuterium exchange process. Thus, cavitating ultrasound likely incorporates a high level of molecular vibrational excitation, suggesting that the vibrational temperature is not in equilibrium with the thermal (e.g., translational) temperature as the chemistry proceeds along a traditional reaction path.
2006. "Accurate Heats of Formation of the "Arduengo-Type" Carbene and Various Adducts Including H2 from ab Initio Molecular Orbital Theory ." Journal of Physical Chemistry A 110(5):1968-1974. doi:10.1021/jp055527i Abstract No abstract is available at this time for this journal article.
2006. "Thermochemical Properties of HxNO Molecules and Ions from ab Initio ElectronicStructure Theory." Journal of Physical Chemistry A 110(1):185-191. doi:10.1021/jp054642q Abstract No abstract is currently available for this journal article.
2006. "High-Resolution Structural Validation of the Computational Redesign of Human U1A Protein ." Structure with Folding & Design 14(5):847-856. doi:doi:10.1016/j.str.2006.02.011 Abstract Achieving atomic-level resolution in the computational design of a protein structure remains a challenging problem despite recent progress. Rigorous experimental tests are needed to improve protein design algorithms, yet studies of the structure and dynamics of computationally designed proteins are very few. The NMR structure and backbone dynamics of a redesigned protein of 96 amino acids are compared here with the design target, human U1A protein. We demonstrate that the redesigned protein reproduces the target structure to within the uncertainty of the NMR coordinates, even as 65 out of 96 amino acids were simultaneously changed by purely computational methods. The dynamics of the backbone of the redesigned protein also mirror those of human U1A, suggesting that the protein design algorithm captures the shape of the potential energy landscape in addition to the local energy minimum.
2006. "Determination of NAPL-Water Interfacial Areas in Well-Characterized Porous Media." Environmental Science and Technology 40(3):815-822. Abstract The nonaqueous-phase liquid (NAPL)-water interfacial area is an important parameter which influences the rate of NAPL dissolution in porous media. The aim of this study was to generate a set of baseline data for specific interfacial area for a two-phase entrapped NAPL-water system in well-characterised porous media, and subsequently use these data to evaluate two current theoretical models. The first model tested distributes entrapped NAPL over the pore classes based on Land’s algorithm and assumes the resulting blobs to be spherical. The other model is thermodynamically based, assuming that reversible work done on the system results in an increase in interfacial area, such that the area between drainage and imbibition retention curves can be related to the interfacial area. Interfacial tracer tests (IFTT) were used to measure specific entrapped NAPL (hexadecane)-water interfacial areas in columns packed with four grades (12/20, 20/30, 30/40, 40/50) of silica sand. Using the anionic surfactant dihexylsulfosuccinate (Aerosol® MA80), IFTT gave specific interfacial areas between 58 cm-1 for the finest sand and 16 cm-1 for the coarsest, compared to values of between 33 cm-1 and 7 cm-1 for the first model and between 19 cm-1 and 5 cm-1 for the thermodynamic model. Results from the literature suggest that non-spherical blobs shapes occur relatively frequently; hence it is reasonable to suggest that the assumption of spherical NAPL blobs may explain the underprediction by the first model. The thermodynamic model underestimates the interfacial area because it assumes that entrapment occurs only within the largest pores. A modified version of the latter model, allowing entrapment across all pore classes, yielded values between 58 cm-1 and 13 cm-1. Of the models tested the modified thermodynamic model best predicts the interfacial area.
2006. "Growth of Epitaxial Thin Pd(111) Films on Pt(111) and Oxygen-Terminated FeO(111) Surfaces ." Surface Science 600(17):3461-3471. doi:10.1016/j.susc.2006.06.036 Abstract Ultra-thin Pd films (1-10 monolayers) were deposited at 30 K on a Pt(111) single crystal and on an oxygen-terminated FeO(111) monolayer supported on Pt(111). Low energy electron diffraction, Auger electron spectroscopy, and Kr and CO temperature programmed desorption techniques were used to investigate the annealing induced changes in the film surface morphology. For growth on Pt(111), the films order upon annealing to 500 K and form epitaxial Pd(111). Further annealing above 900 K results in Pd diffusion into the Pt(111) bulk and Pt-Pd alloy formation. Chemisorption of CO shows that even the first ordered monolayer of Pd on Pt(111) has adsorption properties identical to bulk Pd(111). Similar experiments conducted on FeO(111) indicate that 500 K annealing of a 10 ML thick Pd deposit also yields ordered Pd(111). In contrast, annealing of 1 and 3 ML thick Pd films did not result in formation of continuous Pd(111). We speculate that for these thinner films Pd diffuses underneath the FeO(111).
2006. "Physisorption of N2, O2, and CO on Fully Oxidized TiO2(110)." Journal of Physical Chemistry B 110(12):6229-6235. doi:10.1021/jp0564905 Abstract Physisorption of N2, O2 and CO was studied on fully oxidized TiO2(110) using beam reflection and temperature programmed desorption (TPD) techniques. Sticking coefficients for all three molecules are nearly equal (0.75 ± 0.05) and approximately independent of coverage suggesting that adsorption occurs via a precursor mediated mechanism. Excluding multilayer coverages, the TPD spectra for all three adsorbates exhibit three distinct coverage regimes that can be interpreted in accord with previous theoretical studies of N2 adsorption. At low coverages (0 to 0.5 N2/Ti4+), N2 molecules bind head-on to five-coordinated Ti4+ ions. The adsorption occurs preferentially on the Ti4+ sites that do not have neighboring adsorbates. This arrangement minimizes the repulsive interactions between the adsorbed molecules along the Ti4+ rows resulting in a relatively small shift of the TPD peak (105 → 90 K) with increasing coverage. At higher N2 coverages (0 to 1.0 N2/Ti4+) the nearest-neighbor Ti4+ sites become occupied. The close proximity of the adsorbates results in strong repulsion thus giving rise to a significant shift of the TPD leading edges (90 → 45 K) with increasing coverage. For N2/Ti4+ > 1, an additional low temperature peak (~ 43 K) is present and is ascribed to N2 adsorption on bridge-bonded oxygen rows. The results for O2 and CO are qualitatively similar. The repulsive adsorbate-adsorbate interactions largest for CO, most likely due to aligned CO dipole moments. The coverage dependent binding energies of O2, N2, and CO are determined by inverting TPD profiles.
2006. "Characterization of the structural and electronic properties of crystalline lithium silicates." Journal of Physical Chemistry B 110:22346-22352. doi:10.1021/jp056879s Abstract Structures of several lithium silicate crystals were fully optimized by minimizing the total energy with respect to atom position and lattice parameters using density functional theory (DFT) calculations within the generalized gradient approximation (GGA). Electronic density of states and atomic charges were calculated on the optimized structures. The relative stability of two forms of lithium disilicate determined from density functional theory calculations agree well with experimental results. Partial electronic density of states of different elements and crystallographical sites were determined. The results show bridging and non-bridging oxygen (oxygen ions that bond to two or one silicon ions, respectively) have distinguishable contributions to the oxygen 2s and upper valence bands. Hirshfeld and Bader population analysis were performed to obtain atomic charges of the crystals. Combining the understanding of the silicate crystal chemistry, we found that the Hirshfeld method correctly predicts relative charges of bridging and non-bridging oxygen ions thus provide additional evidence that the Hirshfeld charges better represent the bond ionicity of the silicon-oxygen bonds.
2006. "Short- and medium-range structure of amorphous zircon from molecular dynamics simulations." Physical Review. B, Condensed Matter 74(21):art. no.:214204, (14 pages). doi:10.1103/PhysRevB.74.214204 Abstract We have obtained new insights into the structure of amorphous zircon using classical molecular dynamics simulations with a partial charge model. We present detailed structural characterizations of the simulated high and low density amorphous zircon and compare our results with available neutron diffraction, EXAFS, NMR and other experimental results. The results show that amorphization leads to polymerization of the silicon-oxygen network and the formation of regions rich in zirconium. The average n value of Qn species is 1.6-1.8. A considerable percentage of the oxygen ions (around 20%) have only zirconium in the first coordination shell (free oxygen) in amorphous zircon. The Zr-O bond length (around 2.10Å) is shorter and the oxygen coordination number around zirconium smaller (6-7) than those in crystalline zircon, in good agreement with the EXAFS results. The total structure factors of simulated amorphous zircon also agree well with neutron diffraction results. We have examined the effects of the simulation cell size and relative density on the amorphous structure. The general features such as polymerization of silicon-oxygen network and the formation of clustered zirconium rich regions appear to be independent of system size and volume expansion in the range of 11 to 18%. Based on the obtained amorphous zircon structure, experimentally observed lower chemical durability of amorphous zircon compared to its crystalline form can be explained by the existence of the silicon-oxygen networks and zirconium rich regions in amorphous zircon that provides diffusion channels and eases dissolution processes. Battelle operates PNNL for the USDOE
2006. "Structure, Dynamics, and Electronic Properties of Lithium Disilicate Melt and Glass." Journal of Chemical Physics 125(11):114702/12. doi:10.1063/1.2345060 Abstract Ab initio molecular dynamics simulations within the framework of density functional theory (DFT) have been performed to study the structural, dynamic and electronic properties of lithium disilicate melt and the glass derived from quenching the melt. It is found that lithium ions have a much higher diffusion coefficient and show different diffusion mechanism than the network forming silicon and oxygen ions in the melt. The simulated lithium disilicate glass structure has 100% four coordinated silicon, close to theoretical non-bridging oxygen (NBO) to bridging oxygen (BO) ratio (2:3), and a Qn distribution of 20.8%, 58.4% and 20.8% for n=2,3,4 respectively. In the melt there are considerable amount (10-15%) of silicon coordination defects; however, the average silicon coordination number remains about 4, similar to that in the glass. The lithium ion coordination number increases from 3.7 in the glass to 4.4 in the melt mainly due to the increase of bridging oxygen in the first coordination shell. The bond length and bond angle distributions, vibrational density of states, and static structure factors of the simulated glass were determined where the latter was found to be in good agreement with experiment. Atomic charges were obtained based on Bader and Hirshfeld population analyses. The average Bader charges found in lithium disilicate glass were –1.729, 3.419, and 0.915 for oxygen, silicon and lithium, respectively. The corresponding Hirshfeld charges were –0.307, 0.550, and 0.229. The electronic density of states of the melt and glass were calculated and compared with those of crystalline lithium disilicate. Battelle operates PNNL for the USDOE
2006. "Formation of Cu2O Quantum Dots on SrTiO3 (100): Self-Assembly and Directed Self-Assembly." Journal of Applied Physics 100(9):Art. No. 094315. doi:10.1063/1.2364038 Abstract Nanoscale islands of Cu2O have been synthesized on single-crystal SrTiO3 (100) substrates using oxygen plasma-assisted molecular-beam epitaxy (OPA-MBE). Island growth location has been controlled by using an ex-situ Ga+ focused ion beam (FIB) to modify the growth surface in discrete locations prior to island synthesis. Analysis of Cu2O dot growth on unmodified substrate regions revealed an evolution of dot size and array density. Atomic force microscopy studies show that certain FIB substrate modification and MBE growth condition combinations lead to directed self-assembly of islands. Islands initially formed in the FIB-generated surface topography and filled those features before nucleating on neighboring unmodified surface regions.