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Towards Rational Design of Biosynthesis PathwaysAlazmi, Meshari 19 November 2018 (has links)
Recent advances in genome editing and metabolic engineering enabled a precise construction of de novo biosynthesis pathways for high-value natural products. One important design decision to make for the engineering of heterologous biosynthesis systems is concerned with which foreign metabolic genes to introduce into a given host organism. Although this decision must be made based on multifaceted factors, a major one is the suitability of pathways for the endogenous metabolism of a host organism, in part because the efficacy of heterologous biosynthesis is affected by competing endogenous pathways. To address this point, we developed an open-access web server called MRE (metabolic route explorer) that systematically searches for promising heterologous pathways by considering competing endogenous reactions in a given host organism. MRE utilizes reaction Gibbs free energy information. However, 25% of the reactions do not have accurate estimations or cannot be estimated. To address this issue, we developed a method called FC (fingerprint contribution) to provide a more accurate and complete estimation of the reaction free energy.
To rationally design a productive heterologous biosynthesis system, it is essential to consider the suitability of foreign reactions for the specific endogenous metabolic infrastructure of a host. For a given pair of starting and desired compounds in a given chassis organism, MRE ranks biosynthesis routes from the perspective of the integration of new reactions into the endogenous metabolic system. For each promising heterologous biosynthesis pathway, MRE suggests actual enzymes for foreign metabolic reactions and generates information on competing endogenous reactions for the consumption of metabolites. The URL of MRE is http://www.cbrc.kaust.edu.sa/mre/. Accurate and wide-ranging prediction of thermodynamic parameters for biochemical reactions can facilitate deeper insights into the workings and the design of metabolic systems. Here, we introduce a machine learning method, referred to as fingerprint contribution (FC), with chemical fingerprint-based features for the prediction of the Gibbs free energy of biochemical reactions. From a large pool of 2D fingerprint-based features, this method systematically selects a small number of relevant ones and uses them to construct a regularized linear model. FC is freely available for download at http://sfb.kaust.edu.sa/Pages/Software.aspx.
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Methods for calculating the free energy of atomic clusters /Amon, Lynn, January 2000 (has links)
Thesis (Ph. D.)--University of Washington, 2000. / Vita. Includes bibliographical references (leaves 105-110).
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Gibbs free energy minimization for flow in porous mediaVenkatraman, Ashwin 25 June 2014 (has links)
CO₂ injection in oil reservoirs provides the dual benefit of increasing oil recovery as well as sequestration. Compositional simulations using phase behavior calculations are used to model miscibility and estimate oil recovery. The injected CO₂, however, is known to react with brine. The precipitation and dissolution reactions, especially with carbonate rocks, can have undesirable consequences. The geochemical reactions can also change the mole numbers of components and impact the phase behavior of hydrocarbons. A Gibbs free energy framework that integrates phase equilibrium computations and geochemical reactions is presented in this dissertation. This framework uses the Gibbs free energy function to unify different phase descriptions - Equation of State (EOS) for hydrocarbon components and activity coefficient model for aqueous phase components. A Gibbs free energy minimization model was developed to obtain the equilibrium composition for a system with not just phase equilibrium (no reactions) but also phase and chemical equilibrium (with reactions). This model is adaptable to different reservoirs and can be incorporated in compositional simulators. The Gibbs free energy model is used for two batch calculation applications. In the first application, solubility models are developed for acid gases (CO₂ /H2 S) in water as well as brine at high pressures (0.1 - 80 MPa) and high temperatures (298-393 K). The solubility models are useful for formulating acid gas injection schemes to ensure continuous production from contaminated gas fields as well as for CO₂ sequestration. In the second application, the Gibbs free energy approach is used to predict the phase behavior of hydrocarbon mixtures - CO₂ -nC₁₄ H₃₀ and CH₄ -CO₂. The Gibbs free energy model is also used to predict the impact of geochemical reactions on the phase behavior of these two hydrocarbon mixtures. The Gibbs free energy model is integrated with flow using operator splitting to model an application of cation exchange reactions between aqueous phase and the solid surface. A 1-D numerical model to predict effluent concentration for a system with three cations using the Gibbs free energy minimization approach was observed to be faster than an equivalent stoichiometric approach. Analytical solutions were also developed for this system using the hyperbolic theory of conservation laws and are compared with experimental results available at laboratory and field scales. / text
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Free energy functions in protein structural stability and folding kinetics /Morozov, Alexandre V., January 2003 (has links)
Thesis (Ph. D.)--University of Washington, 2003. / Vita. Includes bibliographical references (p. 96-115).
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Molecular Dynamics Study of Novel Cryoprotectants and of CO2 Capture by sI Clathrate HydratesNohra, Michael 17 July 2012 (has links)
The first project in this work used classical molecular dynamics to study the ice recrystallization inhibition potential of a series of carbohydrates and alcochols, using the hydration index, partial molar volumes and isothermal compressibilities as parameters for measuring their cryogenic efficacy. Unfortunately, after 8 months of testing, this work demonstrates that the accuracy and precision of the density extracted from simulations is not sufficient in providing accurate partial molar volumes. As a result, this work clearly demonstrates that current classical molecular dynamics technology cannot probe the volumetric properties of interest with sufficient accuracy to aid in the research and development of novel cryoprotectants.The second project in this work used molecular dynamics simulations to evaluate the Gibbs free energy change of substituting CO2 in sI clathrate hydrates by N2,CH4, SO2 and H2S flue gas impurities under conditions proposed for CO2 capture (273 K, 10 bar). Our results demonstrate that CO2 substitutions by N2 in the small sI cages were thermodynamically favored. This substitution is problematic in terms of efficient CO2 capture, since the small cages make up 25% of the sI clathrate cages, therefore a significant amount of energy could be spent on removing N2 from the flue gas rather than CO2. The thermodynamics of CO2 substitution by CH4, SO2 and H2S in sI clathrate hydrates was also examined. The substitution of CO2 by these gases in both the small and large cages were determined to be favorable. This suggests that these gases may also disrupt the CO2 capture by sI clathrate hydrates if they are present in large concentrations in the combustion flue stream. Similar substitution thermodynamics at 200 K and 10 bar were also studied. With one exception, we found that the substitution free energies do not significantly change and do not alter the sign of thermodynamics. Thus, using a lower capture temperature does not significantly change the substitution free energies and their implications for CO2 capture by sI clathrate hydrates.
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Energetics of ligand binding to activate site of glutathione transferase M1-1Kinsley, Nichole Michelle 14 November 2006 (has links)
Student Number : 0002483R -
MSc dissertation -
School of Molecular and Cell Biology -
Faculty of Science / Isothermal titration calorimetry was used to investigate the forces that drive ligand
binding to the active site of rGST M1-1. In an attempt to gain insight into the
recognition of non-substrate ligands by GSTs, this study also investigates interactions
between rGST M1-1 and ANS, a non-substrate ligand. At 25 °C, complex formation
between rGST M1-1 and GSH, GSO3
-, and S-hexylglutathione is characterised by a
monophasic binding isotherm with Kd values of 38.5 mM, 2.1 mM and 0.2 mM,
respectively. One molecule of each ligand is bound per monomer of rGST M1-1.
Binding of these ligands is enthalpically favourable and entropically unfavourable
with a resultant favourable Gibbs free energy, overall. The effects of temperature and
buffer ionisation on the energetics of binding were studied. The enthalpic and
entropic contributions for all three ligands exhibited temperature dependence over the
temperature range investigated (5-30 °C). The Gibbs free energy showed negligible
changes with increasing temperature due to enthalpy-entropy compensation. The
temperature dependence of the binding enthalpy yielded heat capacity changes of –
2.69 kJ/mol/K and –3.68 kJ/mol/K at 25 °C for GSH and S-hexylglutathione binding
and –1.86 kJ/mol/K overall for GSO3
-. The linear dependence of DH on temperature
for GSO3
- binding to rGST M1-1 suggests the formation of a more constrained
complex which limits the fluctuations in conformations of the mu-loop at the active
site. The non-linear dependence of DH on temperature for GSH and Shexylglutathione
binding to the enzyme suggests the formation of a complex that
samples different bound conformations due to the mobility of the mu-loop even after
ligand is bound. Calorimetric binding experiments in various buffer systems with
different ionisation enthalpies suggest that the binding of GSH to rGST M1-1 is
coupled to the deprotonation of the thiol of GSH while GSO3
- binding to rGST M1-1
is independent of the buffer ionisation. At 25 °C, the rGST M1-1#1;ANS association is
represented by a monophasic binding isotherm with one molecule of ANS bound per
monomer of rGST M1-1. The interaction is both enthalpically and entropically driven
with a Kd value of 27.2 mM representing moderate affinity. The effect of temperature
on the interaction was investigated over the temperature range of 5-30 °C. The linear
dependence of the binding enthalpy on temperature indicates that no significant
structural changes occur upon binding of ANS to the enzyme (DCp = -0.34 kJ/mol/K).
The change in heat capacity associated with the interaction can be attributed to the burial of the polar sulphonate group of ANS and the exposure of the anilino and
naphthyl rings to solvent as well as the possibility of weak electrostatic interactions
between ANS and residues at the active site. The effect of ethacrynic acid, GSH,
GSO3
- and S-hexylglutathione on the fluorescence of ANS was investigated in order
to obtain some idea as to the location of the ANS binding site on rGST M1-1. ANS
was displaced by GSO3
-, S-hexylglutathione and ethacrynic acid, while no
displacement occurred upon binding of GSH to the active site of rGST M1-1.
Displacement studies and molecular docking simulations indicate that ANS binds to
the H-site of rGST M1-1 and the possibility of a second binding site for the molecule
cannot be ruled out.
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Effect of low-temperature argon matrices on the IR spectra and structure of flexible N-acetylglycine moleculesStepanian, S. G., Ivanov, A. Yu., Adamowicz, L. 12 1900 (has links)
A study of how the matrix environment impacts the structure and IR spectra of N-acetylglycine conformers. The conformational composition of this compound is determined according to an analysis of the FTIR spectra of N-acetylglycine isolated in low temperature argon matrices. Bands of three N-acetylglycine conformers are identified based on the spectra: one major and two minor. The structure of all observed conformers is stabilized by different intramolecular hydrogen bonds. The Gibbs free energies of the conformers were calculated (CCSD(T)/CBS method), and these energy values were used to calculate conformer population at a temperature of 360 K, of which 85.3% belonged to the main conformer, and 9.6% and 5.1% to the minor conformers. We also determined the size and shape of the cavities that form when the N-acetylglycine conformers are embedded in the argon crystal during matrix deposition. It is established that the most energetically favorable cavity for the planar main conformer is the cavity that forms when 7 argon atoms are replaced. At the same time, bulky minor conformers were embedded into cavities that correspond to 8 removed argon atoms. We calculated the complexation energy between argon clusters and conformers, and the deformation energy of the argon crystal and the N-acetylglycine conformers. The matrix-induced shifts to the conformer oscillation frequency are calculated. Published by AIP Publishing.
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Computational petrology: Subsolidus equilibria in the upper mantleSommacal, Silvano, silvano.sommacal@anu.edu.au January 2004 (has links)
Processes that take place in the Earths mantle are not accessible to direct observation. Natural samples of mantle material that have been transported to the surface as xenoliths provide useful information on phase relations and compositions of phases at the pressure and temperature conditions of each rock fragment. In the past, considerable effort has been devoted by petrologists to investigate upper mantle processes experimentally. Results of high temperatures, high pressure experiments have provided insight into lower crust-upper mantle phase relations as a function of temperature, pressure and composition. However, the attainment of equilibrium in these experiments, especially in complex systems, may be very difficult to test rigorously. Furthermore, experimental results may also require extrapolation to different pressures, temperatures or bulk compositions. More recently, thermodynamic modeling has proved to be a very powerful approach to this problem, allowing the deciphering the physicochemical conditions at which mantle processes occur. On the other hand, a comprehensive thermodynamic model to investigate lower crust-upper mantle phase assemblages in complex systems does not exist. ¶
In this study, a new thermodynamic model to describe phase equilibria between silicate and/or oxide crystalline phases has been derived. For every solution phase the molar Gibbs free energy is given by the sum of contributions from the energy of the end-members, ideal mixing on sites, and excess site mixing terms. It is here argued that the end-member term of the Gibbs free energy for complex solid solution phases (e.g. pyroxene, spinel) has not previously been treated in the most appropriate manner. As an example, the correct expression of this term for a pyroxene solution in a general (Na-Ca-Mg-Fe2+-Al-Cr-Fe3+-Si-Ti) system is presented and the principle underlying its formulation for any complex solution phase is elucidated.¶
Based on the thermodynamic model an algorithm to compute lower crust-upper mantle phase equilibria for subsolidus mineral assemblages as a function of composition, temperature and pressure has been developed. Included in the algorithm is a new way to represent the total Gibbs free energy for any multi-phase complex system. At any given temperature and pressure a closed multi-phase system is at its equilibrium condition when the chemical composition of the phases present in the system and the number of moles of each are such that the Gibbs free energy of the system reaches its minimum value. From a mathematical point of view, the determination of equilibrium phase assemblages can, in short, be defined as a constrained minimization problem. To solve the Gibbs free energy minimization problem a Feasible Iterate Sequential Quadratic Programming method (FSQP) is employed. The systems Gibbs free energy is minimized under several different linear and non-linear constraints. The algorithm, coded as a highly flexible FORTRAN computer program (named Gib), has been set up, at the moment, to perform equilibrium calculations in NaO-CaO-MgO-FeO-Al2O3-Cr2O3-Fe2O3- SiO2-TiO2 systems. However, the program is designed in a way that any other oxide component could be easily added.¶
To accurately forward model phase equilibria compositions using Gib, a precise estimation of the thermodynamic data for mineral end-members and of the solution parameters that will be adopted in the computation is needed. As a result, the value of these parameters had to be derived/refined for every solution phase in the investigated systems. A computer program (called GibInv) has been set up, and its implementation is here described in detail, that allows the simultaneous refinement of any of the end-member and mixing parameters. Derivation of internally consistent thermodynamic data is obtained by making use of the Bayesian technique. The program, after being successfully tested in a synthetic case, is initially applied to pyroxene assemblages in the system CaO-MgO-FeO-Al2O3-SiO2 (i.e. CMFAS) and in its constituent subsystems. Preliminary results are presented.¶
The new thermodynamic model is then applied to assemblages of Ca-Mg-Fe olivines and to assemblages of coexisting pyroxenes (orthopyroxene, low Ca- and high Ca clinopyroxene; two or three depending on T-P-bulk composition conditions), in CMFAS system and subsystems. Olivine and pyroxene solid solution and end-member parameters are refined, in part using GibInv and in part on a trial and error basis, and, when necessary, new parameters are derived. Olivine/pyroxene phase relations within such systems and their subsystems are calculated over a wide range of temperatures and pressures and compare very favorably with experimental constraints.
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Molecular Dynamics Study of Novel Cryoprotectants and of CO2 Capture by sI Clathrate HydratesNohra, Michael 17 July 2012 (has links)
The first project in this work used classical molecular dynamics to study the ice recrystallization inhibition potential of a series of carbohydrates and alcochols, using the hydration index, partial molar volumes and isothermal compressibilities as parameters for measuring their cryogenic efficacy. Unfortunately, after 8 months of testing, this work demonstrates that the accuracy and precision of the density extracted from simulations is not sufficient in providing accurate partial molar volumes. As a result, this work clearly demonstrates that current classical molecular dynamics technology cannot probe the volumetric properties of interest with sufficient accuracy to aid in the research and development of novel cryoprotectants.The second project in this work used molecular dynamics simulations to evaluate the Gibbs free energy change of substituting CO2 in sI clathrate hydrates by N2,CH4, SO2 and H2S flue gas impurities under conditions proposed for CO2 capture (273 K, 10 bar). Our results demonstrate that CO2 substitutions by N2 in the small sI cages were thermodynamically favored. This substitution is problematic in terms of efficient CO2 capture, since the small cages make up 25% of the sI clathrate cages, therefore a significant amount of energy could be spent on removing N2 from the flue gas rather than CO2. The thermodynamics of CO2 substitution by CH4, SO2 and H2S in sI clathrate hydrates was also examined. The substitution of CO2 by these gases in both the small and large cages were determined to be favorable. This suggests that these gases may also disrupt the CO2 capture by sI clathrate hydrates if they are present in large concentrations in the combustion flue stream. Similar substitution thermodynamics at 200 K and 10 bar were also studied. With one exception, we found that the substitution free energies do not significantly change and do not alter the sign of thermodynamics. Thus, using a lower capture temperature does not significantly change the substitution free energies and their implications for CO2 capture by sI clathrate hydrates.
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Electrochemical partitioning of actinides and rare earths in molten salt and cadmium solvents activity coefficients and equilibrium simulation /Bechtel, Tom B. January 1997 (has links)
Thesis (Ph. D.)--University of Missouri-Columbia, 1997. / Typescript. Vita. Includes bibliographical references (leaves 180-182). Also available on the Internet.
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