Gotowa bibliografia na temat „Computational Chemistry Method”

With detailed chemical kinetics being employed in combustion simulations, its major computational challenge is the time-intensive nature of chemical kinetics integration due to the large number of chemical species and wide range of chemical timescales involved. In this work, an extended tabulated dynamic chemistry approach with dynamic pruning method is carried out to simulate complex spray combustion for non-premixed combustion process. The thought of extended tabulated dynamic chemistry approach with dynamic pruning is achieved by selecting the optimum acceleration method as well as its error tolerances at different combustion stages depending on combustion characteristics involving the low-temperature combustion. The present method is applied to realistically complex combustion systems involving spray flame of n-heptane fuel and non-premixed combustion engine. Computation efficiency of the proposed method is compared with the results using different accelerating methods, including dynamical adaptive chemistry, in situ adaptive tabulation, and coupled method of tabulated dynamical adaptive chemistry. The results show that transient computational cost will decrease for low-temperature combustion by reducing ambient oxygen concentration clearly in spray flame. Meanwhile, very low computational efficiency is presented once the autoignition occurs, especially at the initial oxygen concentration of 21%. Based on the feature, extended tabulated dynamic chemistry approach with dynamic pruning with different dynamic adaptive chemistry error tolerances is proposed to improve computational efficiency. Extended tabulated dynamic chemistry approach with dynamic pruning with larger error tolerance [Formula: see text] improves around two times for decreased amplitude of transient computational cost at high-temperature combustion stage, and at the same time, the computational accuracy is also improved by comparing the important intermediate species obtained by direct integration. For applications in diesel engine, the results show that extended tabulated dynamic chemistry approach with dynamic pruning can accurately capture the first-stage ignition feature that determines the high-temperature combustion stage. In addition, extended tabulated dynamic chemistry approach with dynamic pruning with the smaller in situ adaptive tabulation error tolerance of 0.001 only used at the high-temperature combustion stage significantly improves the performance on diesel engine simulation with a larger chemistry mechanism. The present method further significantly improves computational efficiency with an overall speedup factor of 10 with high-accuracy compared with result using direct integration.

This paper reviews the need for reduced chemistry modeling for hypersonic reactive flows, and describes the method of computational singular perturbation which can computationally derive reduced chemistry models for a massively complex reaction system.

AbstractWe study weighted ensemble, an interacting particle method for sampling distributions of Markov chains that has been used in computational chemistry since the 1990s. Many important applications of weighted ensemble require the computation of long time averages. We establish the consistency of weighted ensemble in this setting by proving an ergodic theorem for time averages. As part of the proof, we derive explicit variance formulas that could be useful for optimizing the method.

The development of computational research methods and its application in chemistry has been described in this paper. Based on theoretical review on computational research, the study applied experimental research method. The discussion of findings showed that, the development of computational research methods have both advantages and disadvantages that have clearly highlighted in this study.

An efficient semi-implicit numerical method is developed for solving the detailed chemical kinetic source terms in internal combustion (IC) engine simulations. The detailed chemistry system forms a group of coupled stiff ordinary differential equations (ODEs), which presents a very stringent time-step limitation when solved by standard explicit methods, and is computationally expensive when solved by iterative implicit methods. The present numerical solver uses a stiffly stable noniterative semi-implicit method. The formulation of numerical integration exploits the physical requirement that the species density and specific internal energy in the computational cells must be non-negative, so that the Lipschitz time-step constraint is not present and the computation time step can be orders of magnitude larger than that possible in standard explicit methods. The solver exploits the characteristics of the stiffness of the ODEs by using a sequential sort algorithm that ranks an approximation to the dominant eigenvalues of the system to achieve maximum accuracy. Subcycling within the chemistry solver routine is applied for each computational cell in engine simulations, where the subcycle time step is dynamically determined by monitoring the rate of change of concentration of key species, which have short characteristic time scales and are also important to the chemical heat release. The chemistry solver is applied in the KIVA-3V code to diesel engine simulations. Results are compared to those using the CHEMKIN package, which uses the VODE implicit solver. Good agreement was achieved for a wide range of engine operating conditions, and 40-70% CPU time savings were achieved by the present solver compared to the standard CHEMKIN.

<p class="Abstract">Study on the development of computational-based visualization method in Physical Chemistry practical course has been carried out. The study was carried out by combining the conventional method and the visualization using the software. This combination class then was compared to the conventional class of the practical course. The cognitive evaluation showed that the distribution of students’ understanding for the supporting theory of the practical course was not significantly different. The students had relatively the same level of understanding regarding the supporting theory. The evaluation of learning outcomes and the distribution of final grade showed that the class which combined the conventional and visualization method gave a positive result in the learning process</p>

In this era, molecular dynamics and Monte Carlo methods have become the primary simulation methods. With the emergence of computer simulation research methods, it has been possible to solve the sizeable computational volume and some other problems in the simulation process. At present, molecular dynamics simulations have taken an essential place in the substantial computational system and have a remarkable ability to solve multi-body problems. Therefore, researchers widely use it in many fields such as physics, chemistry, and materials science. Meanwhile, the Monte Carlo method is also a very effective statistical simulation method. This method can far surpass ordinary integration in efficiency with guaranteed computational accuracy. Furthermore, the derived kinetic Monte Carlo method can simulate and study dynamics problems. It can be seen that both simulation methods play an vital role in various disciplines. Therefore, it is very significant to understand the mathematical principles behind them and to know their advantages and disadvantages.

Organic chemistry is a theme not so easy to understand by undergraduating students. The motivation of this work was carried out computational study of three different molecules by molecular modeling using classic and semi-empirical methods besides open-source softwares. The optimized structures were visualized through 3D representations which made the study more understanding. Physical chemistry properties were extracted from all molecules. For the molecule one there was good correlation between the calculation methods. For the molecule two and more complex structures like molecule three and four there was possible influence of steric effect showing that each method is applicable for each study system.

Breast cancer is the second largest number of cancer cases in Indonesia, after cervical cancer. The growth of these cancer cells can be prevented with compounds Pentagamavunon-0 (PGV-0) and Pentagamavunon-1 (PGV-1). This compound is an analog of curcumin compounds that have anti breast cancer activity. Modeling the structure of compound PGV-0 and PGV-1 through computational chemistry methods Ab-initio HF/4-31G could be used to predict the geometry and structure elucidation spectra associated with pharmacological activity such as anticancer compounds theoretically.This research involves modeling the structures and spectra prediction calculation compounds PGV-0 and PGV-1 by computational chemistry methods Ab-initio HF/4-31G, using Gaussian03W. The result using Ab-initio HF/4-31G method then compared with data from experimental geometry and the results of calculations with AM1.The results showed that computational chemistry methods Ab-initio HF/4-31G calculations give better results for modeling the structure compared semiempirik method AM1.

Ionization in flames is of interest in the design and development of modern combustion devices. The identity and concentration of various charged species in reacting mixtures can play an important role in the diagnostics and control of such devices. Simplified chemistry computations that provide good estimates of ionic species in complex flow-fields can be used to model turbulent reacting flows in various combustion devices, greatly reducing the required computational resources for design and development studies. A critical assessment of the use of the equilibrium chemistry method to compute charged species concentration in combusting mixtures under various temperatures, pressures, and thermal disequilibrium conditions is presented. The use of equilibrium chemistry to compute charged species concentrations in propane-air mixtures performed by Calcote and King has been extended. A more accurate computational methodology that includes the effect of negative ions, chemi-ions (H3O+ and CHO+), and thermal nonequilibrium was investigated to evaluate the suitability of equilibrium computations for estimating charged species concentrations in reacting mixtures. The results show that equilibrium computations which include the effects of H3O+ and elevated electron temperatures can indeed explain the levels of ion concentrations observed in laboratory flame experiments under lean and near-stoichiometric conditions. Furthermore, under engine-like conditions at higher temperatures and pressures, equilibrium computations can be used to obtain useful estimates of charged species concentrations in modern combustion devices.

Brief explanation and history of cinchona based Phase Transfer Catalysis (PTC). Studied aryl acetates in PTC, encompassing napthoyl, 6-methoxy napthoyl, phenyl and protected 4-hydroxy phenyl acetates. Investigated means of controlling the selectivity of the PTC reaction by changing the electrophile size, the ether side group size or by addition of inorganic salts. Found that either small or aromatic electophiles increased enantioselectivity more than aliphatic electrophiles, and that increasing the size of ether protecting group also increased selectivity. Positive effects of salt addition included either decreasing reaction time or increasing enantiomeric excess. Applied findings towards the synthesis of S-equol. Computational experiments working towards deducing the transition state between PTC and aryl acetate substrates.

Solubility is the concentration of a solute in a saturated solution at a given temperature and pressure. Solubility of a drug in aqueous media is a pre-requisite to achieve desired concentration of a drug in the systemic circulation. Low aqueous solubility is a major problem encountered with formulation development of recently designed new chemical entities. Solubility of poorly soluble drugs is enhanced by physical and chemical modifications of drug. Shake flask method is the most commonly used experimental method to determine solubility. However, this method has several limitations. A single solubility experiment can go on for several days and even weeks. Besides this, a large amount of drug is required to carry out the experiment. In order to overcome this and make initial screening easier, computational method can be used to predict solubility. In this study, the solubility of 12 small molecules of BCS class II having a wide range of physicochemical properties were studied to enhance their solubility by hot melt method. Three different grades of PEG (1450, 4000, 8000), PVP K17 and Urea as the hydrophilic carriers was employed for the solubility enhancement. The overall objective of this investigation is to develop a model that could estimate enhanced solubility using physicochemical descriptors. Multiple linear regression (MLR), a statistical tool, was used to generate a equation for the solubility by correlating physicochemical properties of the drug like- molecular size, logP, pKa, HBA, HBD, melting point, polar surface area, and number of rotatable bonds. Solubility enhancement is also influenced by the carrier used, we included the physicochemical properties of the carriers like molecular weight and solubility parameter in the development of the model. MLR analysis model, resulted in an equation, where, Log solubility = 5.982-0.010 MW (drug)-0.452 LogP-0.320 HBA-0.095 ?solubility parameter+0.015 MV. A regression analysis yielded a good fit with a regression value (adjusted R2) of 0.74. The model has been validated by leave one out method. This model has the potential to estimate the solubility of a physically modified drug in screening stages of drug development.

The data presented in this thesis is a comprehensive study on the nature of peptide structure and how subtle and systematic changes in sequence and sidechain affect the basicity, ion stability, and conformation of a peptide. The peptides characterized were acetylated polyalanine di-, tri-, and tetra- peptides containing a proton-accepting probe: lysine and or the non-proteinogenic lysine-homologs: ornithine, 2,4-diaminobutyric acid, and 2,3-diaminopropionic acid. Peptides were studied in isomeric pairs for which the basic amino acid was placed closest to the N-terminus or the C-terminus of each peptide family (A n Probe vs. ProbeA n ). Using a variety of mass spectrometry based techniques and infrared multiphoton dissociation ion spectroscopy, the isomeric families of polyalanine peptides were characterized. Quantum chemical techniques were employed in parallel to provide theoretical predictions of three-dimensional structure, physical properties (dipole moment, polarizability, and accessible surface area), thermochemical values, and vibrational IR spectra, to gain further understanding of the peptides studied and to push the limits of current theoretical models. Overall it was found that the AnProbe peptide was more basic than their ProbeAn isomer. For the dipeptide systems, the greater basicity of AProbe peptides was due to efficiently charge-solvated ions which formed more compact structures compared to their ProbeA counterpart. For the tri- and tetra- peptide systems, greater basicity of the A 2,3 Probe peptides was likely due to formation of α or 3 10 helix-like structures in the protonated forms., introducing the macrodipolar effect, which cooperatively encouraged helical formation while stabilizing the charged site. On the other hand, ProbeA 2,3 peptides formed charge-solvated coils which do not exhibit any kind of dipole effect, resulting in lower basicity than their A2,3Probe counterpart.

Numerous enzymatic reactions are controlled by the chemistry of metallic ions. This dissertation investigates the electronic properties of three transition metal (copper, chromium, and nickel) complexes and describes modeling studies performed on glutathione synthetase. (1) Copper nitrene complexes were computationally characterized, as these complexes have yet to be experimentally isolated. (2) Multireference calculations were carried out on a symmetric C2v chromium dimer derived from the crystal structure of the [(tBu3SiO)Cr(µ-OSitBu3)]2 complex. (3) The T-shaped geometry of a three-coordinate β-diketiminate nickel(I) complex with a CO ligand was compared and contrasted with isoelectronic and isosteric copper(II) complexes. (4) Glutathione synthetase (GS), an enzyme that belongs to the ATP-grasp superfamily, catalyzes the (Mg, ATP)-dependent biosynthesis of glutathione (GSH) from γ-glutamylcysteine and glycine. The free and reactant forms of human GS (wild-type and glycine mutants) were modeled computationally by employing molecular dynamics simulations, as these currently have not been structurally characterized.

[ES] En este trabajo estudiamos dos reacciones catalíticas relevantes para la industria y la localización del anión fluoruro en la zeolita RTH, sintetizada en medio fluoruro. El capítulo 3 es el primer capítulo de resultados, donde se estudia la reducción quimioselectiva del nitroestireno en las superficies Ni(111), Co(111), Cu(111) y Pd(111). El mecanismo generalmente aceptado de esta reacción está basado en el esquema propuesto por Haber en 1898, en el que la reacción puede transcurrir por dos rutas, la directa y la de condensación. En este capítulo exploramos ambas rutas, y observamos que la ruptura de los enlaces N-O y la consecuente formación de enlaces metal-O está más favorecida que la formación de enlaces N-H en las superficies Ni(111) y Co(111), debido al carácter oxofílico de ambos metales. Las etapas más lentas involucran la formación de enlaces N-H. En las superficies de metales nobles como Pt(111) y Pd(111) se observa el comportamiento contrario. La superficie Cu(111) es un caso intermedio comparado con los metales nobles y no nobles. Además, el nitroestireno interactúa con los átomos de Cu de la superficie solo a través de grupo nitro, con lo cual es un candidato ideal para alcanzar selectividades cerca del 100%. Sin embargo, la superficie Cu(111) no es capaz de activar la molécula de H2. En este sentido, proponemos un catalizador bimetálico basado en Cu, dopado con otro metal capaz de activar al H2, tales como el Pd o el Ni. En los capítulos 4 y 5 se ha estudiado la reducción catalítica selectiva de los óxidos de nitrógeno (SCR, en inglés) con amoníaco. Usando métodos de DFT, hemos encontrado rutas para la oxidación de NO a NO2, nitritos y nitratos con energías de activación relativamente bajas. También, hemos encontrado que la reducción de Cu2+ a Cu+ requiere la participación simultánea de NO y NH3. Posteriormente, hemos estudiado la influencia del NH3 en este sistema con métodos de dinámica molecular. El NH3 interacciona fuertemente con el Cu+ de forma que dos moléculas de este gas son suficientes para romper la coordinación del catión Cu+ con los oxígenos del anillo 6r, y formar el complejo lineal [Cu(NH3)2]+. Además, los cationes Cu2+ pueden ser estabilizados fuera de la red mediante la formación del complejo tetraamincobre(II). Debido a la presencia de los cationes Cu+ y Cu2+ coordinados a la red de la zeolita, aparecen bandas en la región entre 800-1000 cm-1 del espectro infrarrojo. El análisis de las frecuencias IR de varios modelos con Cu+ y Cu2+ coordinados al anillo 6r, o formando complejos con amoniaco indica que cuando los cationes Cu+ y Cu2+ están coordinados a los oxígenos del anillo 6r aparecen vibraciones entre 830 y 960 cm-1. Frecuencias en esta zona también se obtienen en los casos en que NO, NO2, O2 y combinaciones de dos de ellos están adsorbidos en Cu+ y Cu2+. Sin embargo, cuando los cationes Cu+ y Cu2+ están fuera del anillo (no hay enlaces entre los cationes de cobre y los oxígenos del anillo 6r) no se obtienen vibraciones de IR en esta región del espectro. Estos resultados indican que con el seguimiento del espectro IR durante la reacción SCR es posible determinar si los cationes Cu+ y Cu2+ están coordinados o no al anillo de 6r en las etapas de oxidación y reducción. Por último, hemos simulado el desplazamiento químico de 19F, δiso,, en la zeolita sintetizada RTH. El análisis del δiso de los distintos modelos utilizados nos ha permitido reconocer la simetría del material sintetizado, el cual pertenece al grupo espacial P1 y la nueva celda unidad ha sido confirmada experimentalmente por difracción de rayos X. Finalmente, hemos asignado la señal experimental que aparece en el espectro de 19F a -67.2_ppm, al F- localizado en un sitio T2, el cual es a su vez la posición más estable. Además, la señal a -71.8 ppm se ha asignado al anión F- localizado en un sitio T4.
[CA] En aquest treball estudiem dues reaccions catalítiques rellevants per a la indústria i la localització de l'anió fluorur en la zeolita RTH, sintetitzada al mig fluorur. El capítol 3 és el primer capítol de resultats, on s'estudia la reducció quimioselectiva del nitroestireno en les superfícies Ni(111), Co(111), Cu(111) i Pd(111). El mecanisme generalment acceptat d'aquesta reacció està basat en l'esquema proposat per Haver-hi en 1898, en el qual la reacció pot transcórrer per dues rutes, la directa i la de condensació. En aquest capítol explorem totes dues rutes, i observem que la ruptura dels enllaços N-O i la conseqüent formació d'enllaços metall-O està més afavorida que la formació d'enllaços N-H en les superfícies Ni(111) i Co(111), a causa del caràcter oxofílico de tots dos metalls. Les etapes més lentes involucren la formació d'enllaços N-H. En les superfícies de metalls nobles com Pt(111) i Pd(111) s'observa el comportament contrari. La superfície Cu(111) és un cas intermedi comparat amb els metalls nobles i no nobles. A més, el nitroestireno interactua amb els àtoms de Cu de la superfície sol a través de grup nitre, amb la qual cosa és un candidat ideal per a aconseguir selectivitats prop del 100%. No obstant això, la superfície Cu(111) no és capaç d'activar la molècula d'H2. En aquest sentit, proposem un catalitzador bimetàl·lic basat en Cu, dopat amb un altre metall capaç d'activar a l'H2, com ara el Pd o el Ni. En els capítols 4 i 5 hem estudiat la reducció catalítica selectiva dels òxids de nitrogen (SCR, en anglés) amb amoníac. Usant mètodes de DFT, hem trobat rutes per a l'oxidació de NO a NO2, nitrits i nitrats amb energies d'activació relativament baixes. També, hem trobat que la reducció de Cu2+ a Cu+ requereix la participació simultània de NO i NH3. Posteriorment, hem estudiat la influència del NH3 en aquest sistema amb mètodes de dinàmica molecular. El NH3 interacciona fortament amb el Cu+ de manera que dues molècules d'aquest gas són suficients per a trencar la coordinació del catió Cu+ amb els oxígens de l'anell 6r, i formar el complex lineal [Cu(NH3)2]+. A més, els cations Cu2+ poden ser estabilitzats fora de la xarxa mitjançant la formació del complex tetraamincobre(II). A causa de la presència dels cations Cu+ i Cu2+ coordinats a la xarxa de la zeolita, apareixen bandes a la regió entre 800-1000 cm-1 de l'espectre infraroig. L'anàlisi de les freqüències IR de diversos models amb Cu+ i Cu2+ coordinats a l'anell 6r, o formant complexos amb amoníac indica que quan els cations Cu+ i Cu2+ estan coordinats als oxígens de l'anell 6r apareixen vibracions entre 830 i 960 cm-1. Freqüències en aquesta zona també s'obtenen en els casos en què NO, NO2, O2 i combinacions de dues d'ells estan adsorbidos en Cu+ i Cu2+. No obstant això, quan els cations Cu+ i Cu2+ estan fora de l'anell (no hi ha enllaços entre els cations de coure i els oxígens de l'anell 6r) no s'obtenen vibracions d'IR en aquesta regió de l'espectre. Aquests resultats indiquen que amb el seguiment de l'espectre IR durant la reacció SCR és possible determinar si els cations Cu+ i Cu2+ estan coordinats o no a l'anell de 6r en les etapes d'oxidació i reducció. Finalment, hem simulat el desplaçament químic de 19F, δiso, en la zeolita sintetitzada RTH. L'anàlisi del δiso dels diferents models utilitzats ens ha permés reconéixer la simetria del material sintetitzat, el qual pertany al grup espacial P1 i la nova cel·la unitat ha sigut confirmada experimentalment per difracció de raigs X. Finalment, hem assignat el senyal experimental que apareix en l'espectre de 19F a -67.2 ppm, al F- localitzat en un lloc T2, el qual és al seu torn la posició més estable. A més, el senyal a -71.8 ppm s'ha assignat a l'anió F- localitzat en un lloc T4.
[EN] In this work, we have studied two heterogeneous catalytic reactions and the localization of the fluoride anion in the as-made RTH framework, synthesized in fluoride medium. The first results, included in chapter 3, correspond to the chemoselective reduction of nitrostyrene on different metal surfaces, i.e, Ni(111), Co(111), Cu(111) and Pd(111). Until very recently, the reduction of the nitro group was explained on the basis of the general mechanism proposed by Haber in 1898 where the reaction can follow two routes, the direct and condensation route. We have explored the relevant elementary steps of both routes and found that because of the oxophilic nature of Ni and Co, the steps involving the dissociation of N-O bonds and formation of metal-O bonds are significantly favored compared with the other steps on both metal surfaces. In addition, the most demanding steps in terms of energy involve the formation of N-H bonds. These findings are in contrast to those of noble metals such as Pt and Pd, where the opposite behavior is observed. The behavior of Cu(111) lies in between the aforementioned cases, and also no chemical bonds between the carbon atoms of the aromatic ring of nitrostyrene and the Cu(111) surface is formed. For this reason, it might be an ideal candidate to achieve nearly 100 % selectivity. However, the Cu(111) surface does not seem to activate the H2 molecule. In this regard, we propose a bimetallic Cu-based catalyst whose surface is doped with atoms of a H2-activating metal, such as Ni or Pd. On another matter, we have also investigated the selective catalytic reduction of nitrogen oxides (SCR-NOx) and the main results are presented in the following two chapters, 4 and 5. By using static DFT methods, we found pathways for the oxidation of NO to NO2, nitrites and nitrates with relatively low activation energies. We also found, in agreement with experimental reports, that the reduction of Cu2+ to Cu+ requires the simultaneous participation of NO and NH3. Later, molecular dynamics simulations allowed us to assess the influence of NH3. The strong interaction of NH3 with the Cu+ cation is evidenced by its ability to detach Cu+ from the zeolite framework and form the mobile linear complex [Cu(NH3)2]+. Cu+ is no longer coordinated to the zeolite framework in the presence of two NH3 molecules. This observation and the fact that the T-O-T vibrations of the framework produce bands in the 800-1000 cm-1 region of the IR spectrum when perturbed by the coordination of Cu+ and Cu2+ cations, indicate that bands in the 800-1000 cm-1 regions should be observed when both copper cations are bonded to the framework oxygens. Finally, we have also studied NMR properties of the as-made pure silica RTH framework, aiming at locating the compensating fluoride anion. The calculation of the 19F chemical shift in different T sites and comparison with the experimental NMR spectra shows that the as-made RTH belongs to the P-1 space group with 16 Si, 32 O atoms, one fluoride anion and one OSDA cation. These results have been confirmed experimentally by XRD. In addition, we have assigned the experimental signal of 19F at -67.2 ppm to the fluoride anion in a T2 site, which in turn is the most stable location found, and the signal of -71.8 ppm to a fluoride anion sitting in a T4 site.
My acknowledgements to “La Caixa foundation” for the financial support through “La Caixa−Severo Ochoa” International PhD Fellowships (call 2015), to the Spanish Supercomputing Network (RES), to the Centre de Càlcul de la Universitat de València, to the Flemish Supercomputer Center (VSC) of Ghent University for the computational resources and technical support, and to the Spanish Government through the MAT2017-82288-C2-1-P programme
Millan Cabrera, R. (2021). Computational study of heterogeneous catalytic systems. Kinetic and structural insights from Density Functional Theory [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/161934
TESIS

Enzymes play a crucial role in modern biotechnology, industry, food processing and medical applications. Since their first discovered industrial use, man has attempted to discover new enzymes from Nature to catalyze different chemical reactions. In modern times, with the advent of computational methods, protein structure solutions, protein sequencing and DNA synthesis methods, we now have the tools to enable new approaches to rational enzyme engineering. With an enzyme structure in hand, a researcher may run an in silico experiment to sample different amino acids in the active site in order to identify new combinations which likely stabilize a transition-state-enzyme model. A suggested mutation can then be encoded into the desired enzyme gene, ordered, synthesized and tested. Although this truly astonishing feat of engineering and modern biotechnology allows the redesign of existing enzymes to acquire a new substrate specificity, it still requires a large amount of time, capital and technical capabilities.

Concurrently, while making strides in computational protein design, the cost of sequencing DNA plummeted after the turn of the century. With the reduced cost of sequencing, the number of sequences in public databases of naturally occurring proteins has grown exponentially. This new, large source of information can be utilized to enable rational enzyme design, as long as it can be coupled with accurate modeling of the protein sequences.

This work first describes a novel approach to reengineering enzymes (Genome Enzyme Orthologue Mining; GEO) that utilizes the vast amount of protein sequences in modern databases along with extensive computation modeling and achieves comparable results to the state-of-the-art rational enzyme design methods. Then, inspired by the success of this new method and aware of it's reliance on the accuracy of the protein models, we created a computational benchmark to both measure the accuracy of our models as well as improve it by encoding additional information about the structure, derived from mechanistic studies (Catalytic Geometry constraints; CG). Lastly, we use the improved accuracy method to automatically model hundreds of putative enzymes sequences and dock substrates into them to extract important features that are then used to inform experiments and design. This is used to reengineer a ribonucleotide reductase to catalyze a aldehyde deformylating oxygenase reaction.

These chapters advance the field of rational enzyme engineering, by providing a novel technique that may enable efficient routes to rationally design enzymes for reactions of interest. These chapters also advance the field of homology modeling, in the specific domain in which the researcher is modeling an enzyme with a known chemical reaction. Lastly, these chapters and techniques lead to an example which utilizes highly accurate computational models to create features which can help guide the rational design of enzyme catalysts.

Reactive flow simulations involving turbulence-chemistry interactions can be very challenging because of the strong non-linear coupling between chemistry and fluid dynamics. Furthermore, the chemistry is described with hundreds of reactions, which is prohibitive to solve using computational fluid dynamics (CFD). Using a reduced set of mechanisms that contains a subset of the important species is more practical. However, the species modeled must capture the key combustion characteristics of interest, such as ignition, species distributions and major pollutant formation. Previously, the authors used the joint probability density function (PDF) to study the non-premixed turbulent flames, and continue the work here. New CFD simulations were conducted for a non-premixed turbulent syngas flame using four reduced mechanisms models (3-step, 8-step, 9-step and 12-step reactions) to assess the predictive capabilities in the calculation of turbulence-chemistry interactions. The performance of the different reduced mechanism models was assessed and compared with previous PDF model results and the experimental results of Correa and Gulati (1992, “Measurements and Modeling of a Bluff Body Stabilized Flame,” Combustion and Flame, 89(2)). The predictions of temperature and species from the reduced mechanisms of the 3-step and 8-step were found to have differences as large as 20%. It was also found that the reduced 12-step mechanism was able to represent the strong turbulence-chemistry interactions in the syngas flame and demonstrated good ability of predicting species distribution. Therefore, a simplified chemical mechanism model was successfully developed to simulate the non-premixed syngas flame. The 12-step reduced mechanism will guide other reduced mechanism models for syngas fuels. However, the PDF method still gives the best predictions of temperature and requires the smallest computational time.