Orientador: Pedro Luiz Onófrio Volpe / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Química / Made available in DSpace on 2018-08-16T00:48:59Z (GMT). No. of bitstreams: 1 Camargo_MarceloSilvanode_D.pdf: 5113129 bytes, checksum: 44e51a54bcc1176d6b50d7db1a17558d (MD5) Previous issue date: 2009 / Resumo: O objetivo deste trabalho é o estudo das propriedades locais de soluções líquidas binárias de não-eletrólitos. Para se alcançar tal objetivo, executou-se o cálculo dos valores das integrais de Kirkwood-Buff a partir de grandezas termodinâmicas, elaborado por Ben-Naim. Foram calculados valores para as integrais KB de uma solução de etanol em água a 298,15 K, dando-se especial ênfase a regiões de alta concentração de água. Outras grandezas locais, como o desvio da idealidade em relação a uma solução simétrica, também foram calculadas a partir dos resultados obtidos para as integrais KB. O enfoque diferencial de Koga foi utilizado de maneira a complementar a análise realizada com as integrais de Kirkwood-Buff, possibilitando um estudo mais aprofundado do sistema. Até onde o autor desta dissertação está familiarizado, a utilização conjunta destas duas ferramentas teóricas está sendo implementada pela primeira vez / Abstract: The objective of this work is the study of local properties of binary liquid solutions of non-electrolytes. To achieve this goal, Kirkwood-Buff integrals from thermodynamic quantities were obtained, as Ben-Naim has demonstrated. We obtained the values of Kirkwood-Buff integrals for a solution of ethanol in water at 298.15 K, with particular emphasis on areas of high concentration of water. Other local qantities, as the deviation of ideality with respect to a symmetric solution, were also calculated from the results obtained from KB integrals. Koga¿s Differential approach was used in order to complement the analysis provided by Kirkwood-Buff integrals, allowing further understanding of the system. As far as the author of this thesis is familiar, the joint use / Doutorado / Físico-Química / Mestre em Química

Master of Science / Department of Chemistry / Paul E. Smith / The increasing importance of ion-water interactions in the field of chemistry and biology is leading us to examine the structure and dynamic properties of molecules of interest, based on the application of computer-aided models using molecular dynamics simulations. To enable this type of MD study, a molecular mechanics force field was developed and implemented. Kirkwood-Buff theory has been proved to be a powerful tool to provide a link between molecular quantities and corresponding thermodynamic properties. Parameters are the vital basis of a force field. KB integrals and densities were used to guide the development of parameters which could describe the activity of aqueous solutions of interest accurately. In this work, a Kirkwood-Buff Force Field (KBFF) for MD simulation of ammonium sulfate, sodium sulfate, sodium perchlorate and sodium nitrate are presented. Comparison between the KBFF models and existing force fields for ammonium sulfate was also performed and proved that KBFF is very promising. Not only were the experimentally observed KB integrals and density reproduced by KBFF, but other properties like self diffusion constant and relative permittivity are also well produced.

Les électrolytes liquides, composés d’un sel dissous dans un solvant, interviennent dans la composition des batteries et font l’objet de nombreuses études afin d’améliorer leurs performances et leur sécurité. Parmi toutes les propriétés essentielles d’un électrolyte, la plus importante est sa conductivité ionique, qui influe sur les performances de la batterie. Pour un sel donné, la conductivité est elle-même principalement déterminée par les propriétés physico-chimiques du solvant comme sa constante diélectrique ou sa viscosité. L’objectif de cette étude est de développer des modèles permettant d’estimer des propriétés d’intérêt des électrolytes liquides, afin d’offrir un gain de temps aux chimistes, qui pourront éliminer les compositions inadéquates du point de vue de telle ou telle propriété. La première partie de cette étude présente une méthode pour estimer la conductivité d’un électrolyte, constitué d’un sel LiPF6 dans un mélange de solvants. Cette méthode s’appuie sur de nouvelles équations, pour estimer les paramètres de l’équation de Casteel-Amis, à partir de propriétés physico-chimiques du mélange de solvants, dont la constante diélectrique. La seconde partie présente a par ailleurs permis de développer une méthode pour estimer la constante diélectrique d’un solvant pur, à partir de sa structure chimique. Cette méthode s’appuie sur de nouveaux modèles additifs qui permettent d’estimer les paramètres de l’équation de Kirkwood-Fröhlich. Parmi ces modèles, deux d’entre eux permettent l’estimation de la densité et de l’indice de réfraction d’un composé liquide à température ambiante. L’ensemble des modèles développés sont utilisables via une interface utilisateur. / Liquid electrolytes, composed of a salt dissolved in a solvent, are used in the composition of batteries and are the subject of numerous studies to improve their performance and safety. Of all the essential properties of an electrolyte, the most important is its ionic conductivity, which influences the battery's performance. For a given salt, the conductivity itself is mainly determined by the physico-chemical properties of the solvent such as its dielectric constant or its viscosity. The objective of this study is to develop models to estimate properties of interest of liquid electrolytes, in order to offer time savings to chemists, who will be able to eliminate inadequate compositions from the point of view of such or such property. The first part of this study presents a method to estimate the conductivity of an electrolyte, consisting of a LiPF6 salt in a solvent mixture. This method is based on new equations, to estimate the parameters of the Casteel-Amis equation, based on the physico-chemical properties of the solvent mixture, including the dielectric constant. The second part also presents a method to estimate the dielectric constant of a pure solvent, based on its chemical structure. This method is based on new additive models that estimate the parameters of the Kirkwood-Fröhlich equation. Two of these models estimate the density and refractive index of a liquid compound at room temperature. All the models developed can be used via a user interface.

Master of Science / Department of Biochemistry / Paul E. Smith / We are developing a force field (FF) for molecular dynamics (MD) simulations of peptides and small proteins that is grounded in the Kirkwood-Buff theory of solutions. Here we present the Kirkwood-Buff Force Field (KBFF) parameters for the aromatic amino acids, based upon simulations of binary mixtures of small molecules representative of these amino acids over their entire composition ranges (excluding Histidine). Many aromatics are not fully soluble in water, so they have instead been studied in solvents of methanol or toluene. The parameters were developed by studying the following binary solutions: Phenylalanine − benzene + methanol, toluene + methanol, and toluene + benzene; Tyrosine − toluene + phenol and toluene + p-Cresol; Tryptophan − pyrrole + methanol and indole + methanol; Histidine − pyrrole + methanol, pyridine + methanol, pyridine + water, histidine + water (at 0.25 molal), and histidine monohydrochloride + water (at 0.3 molal and 0.6 molal). Our simulations reproduce the Kirkwood-Buff integrals, which guarantees that the KBFF provides an adequate balance of solute-solvent, solute-solute, and solvent-solvent interactions. Additionally, we show that the KBFF does not sacrifice reproduction of other solution properties in order to achieve this improved description of intermolecular interactions. We present these results as validating evidence for the future use of the KBFF in simulations of peptides and small proteins.

Doctor of Philosophy / Department of Chemistry / Paul E. Smith / The impact of computer simulations has become quite significant especially with the development of supercomputers during the last couple of decades. They are used in a wide range of purposes such as exploring experimentally inaccessible phenomena and providing an alternative when experiments are expensive, dangerous, time consuming, difficult and controversial. In terms of applications in biological systems molecular modeling techniques can be used in rational drug design, predicting structures of proteins and circumstances where the atomic level descriptions provided by them are valuable for the understanding of the systems of interest. Hence, the potential of computer simulations of biomolecular systems is undeniable. Irrespective of the promising uses of computer simulations, it cannot be guaranteed that the results will be realistic. The precision of a molecular simulation depends on the degree of sampling achieved during the simulation while the accuracy of the results depends on the satisfactory description of intramolecular and intermolecular interactions in the system, i.e. the force field. Recently, we have been developing a force field for molecular dynamics simulations of biological systems based on the Kirkwood Buff (KB) theory of solutions, not only with an emphasis on the accurate description of intermolecular interactions, but also by reproducing several physical properties such as partial molar volume, compressibility and composition dependent chemical potential derivatives to match with respective experimental values. In this approach simulation results in terms of KB integrals can be directly compared with experimental data through a KB analysis of the solution properties and therefore it provides a simple and clear method to test the capability of the KB derived force field. Initially, we have provided a rigorous framework for the analysis of experimental and simulation data concerning open and closed multicomponent systems using the KB theory of solutions. The results are illustrated using computer simulations for various concentrations of the solutes Gly, Gly₂ and Gly₃ in both open and closed systems, and in the absence or presence of NaCl as a cosolvent. Then, we have attempted to quantify the interactions between amino acids in aqueous solutions using the KB theory of solutions. The results are illustrated using computer simulations for various concentrations of the twenty zwitterionic amino acids at ambient temperature and pressure. Next, several amino acids were also studied at higher temperatures and pressures and the results are discussed in terms of the preferential (solute over solvent) interactions between the amino acids. Finally, we have described our most recent efforts towards a complete force field for peptides and proteins. The results are illustrated using molecular dynamics simulations of several tripeptides, selected peptides and selected globular proteins at ambient temperature and pressure followed by replica exchange molecular dynamics simulations of a few selected peptides.

Diss.--philosophische Fakultät--Saarbrücken, 1982. / Bibliogr. p. 385-439. Index.

Doctor of Philosophy / Department of Chemistry / Paul E. Smith / Kirkwood Buff (KB) theory is one of the most important theories of solutions. The theory can relate integrals over radial (pair) distribution functions (rdfs) in the grand canonical ensemble to common thermodynamic properties. An inversion of the KB theory has been proposed by Ben-Naim and this has led to the wide spread popularity of KB theory. The idea of the KB inversion procedure is to calculate KB integrals from available thermodynamic properties. The KB theory can be used to validate the force field (ff) parameters used in molecular dynamics simulations. We have tested a series of small molecule ff parameters using KB theory that consists of both atom centered partial atomic charges and extra charge sites. The results indicate that using extra charge sites, derived from QM calculations, does not necessarily provide a more accurate representation of condensed phase properties. A further study aimed at an ongoing project of deriving new biomolecular ff parameters based on KB theory, has developed ff parameters for esters in order to represent the ester conjugation of the phospholipid molecule. The models were further tested against experimental properties. Preferential solvation (PS) is an important concept of solution mixtures that can be described using KB theory. The difference between local composition and bulk composition in solution mixtures leads to the concept of PS. A generalized explanation based on local mole fractions was derived by Ben-Naim using KB theory. However, the original expressions have been modified over years. Here, we propose a new approach based on local volume fractions to explore PS in binary and ternary solution mixtures. Experimental and simulation data were used to examine different approaches to PS. A relationship between the rdf and the triplet distribution function can be obtained using the Kirkwood Superposition Approximation (KSA). A combination of Fluctuation Solution Theory and experimental rdfs are used to examine the KSA at a series of state points for pure water. The accuracy of several other approximate relationships between the pair and triplet correlation functions was also investigated and are in good agreement for regions of the phase diagram where the compressibility is small.

Thesis (MTh)--Stellenbosch University, 2013. / ENGLISH ABSTRACT: The researcher is a minister in a rural congregation in the town of Kirkwood in the Eastern Cape. A growing diversity among congregants became obvious. It led to conflict and challenged the leadership of the congregation to deal with it in a constructive way in order to be a missional congregation that strives to focus on the missio Dei. In order to help the congregation to better understand where it comes from and how it can be used to participate in God’s work in the Sundays River Valley, the researcher described the identity and culture of the congregation as well as the transformation processes that are having such an influence on everybody. The research question is: How can the diversity between congregants be understood, described en used? In Chapter 2 the identity of the congregation is described. Attention is given to Louw’s identity 1996 analysis of the congregation. Afterwards the influence of globalization on the identity of the congregation is described and how it increased the diversity of the congregation. Ethnographic research described the culture of the congregation (Chapter 3). The researcher discussed Armour and Browning’s (2000) Systems theory in Chapter 4. Chapter 5 described the results of empirical research that depicted five of the reigning systems in the congregatation. The data is interpreted and discussed. At the end of each chapter the researcher outlined conclusions. In Chapter 6 these conclusions and the findings of the empirical research are brought to a point on the basis of which a strategy with practical and theological points of departure for the ministry are suggested. The purpose is to guide the congregation to use their diversity in order to fulfill their missional vocation. / AFRIKAANSE OPSOMMING: Die navorser is ʼn dominee in ʼn plattelandse gemeente in Kirkwood in die Oos-Kaap. Hy merk ʼn groeiende diversiteit tussen lidmate van die gemeente ten opsigte van hul lewens- en wêreldbeskouings op. Hierdie diversiteit lei tot konflik en stel die leierskap van die gemeente voor ‘n uitdaging om die diversiteit so te bestuur en te benut. Sodoende kan die gemeente haar roeping om binne hul konteks deel te neem aan die missio Dei bereik. Die studie beskryf die diversiteit. Die navorsingsvraag lui soos volg: Hoe kan die diversiteit tussen lidmate verstaan word, omskryf word en benut word? Die doel van die studie is om die verskillende lewens- en wêreldbeskouings van die lidmate van die NG gemeente Sondagsrivier (Kirkwood) vas te stel. Hiervoor gebruik die navorser die sisteemteorie van dr. Graves soos deur Armour en Browning toegepas op gemeentewees. In Hoofstuk 2 is die identiteit van die gemeente beskryf. Daar is eerstens gelet op Louw se identiteitsanalise wat hy in 1996 onderneem het. Daarna is die invloed wat globalisasie op die identiteit van die gemeente gehad het, beskryf en hoe dit ‘n toename in diversiteit tot gevolg gehad het. Met behulp van etnografiese navorsing is die kultuur van die gemeente in Hoofstuk 3 beskryf. Die navorser bespreek die Sisteemteorie soos uiteengesit in die boek van Armour en Browning (2002) in Hoofstuk 4. Die doel van hierdie hoofstuk is om die sisteemteorie aan die leser bekend te stel en die nut daarvan vir hierdie studie te verduidelik. Hoofstuk 5 verhaal hoe die Sisteemteorie meetinstrument gebruik is. Die data wat verkry is, word geanaliseer en bespreek. Aan die einde van elke hoofstuk is daar gevolgtrekkings gemaak ten opsigte van die diversiteit in die gemeente. In Hoofstuk 6 kry hierdie gevolgtrekkings en die bevindinge van die empiriese navorsing aandag. Op grond hiervan word ‘n strategie met praktiese en teologiese vertrekpunte vir die bedieningspraktyk voorgestel. Dit het ten doel om die gemeente te begelei om hul diversiteit te benut in die uitleef van hulle missionale roeping.

Submitted by Vinicius de Godoi Contessoto null (vinicius@sjrp.unesp.br) on 2016-09-09T18:11:23Z No. of bitstreams: 1 Tese-Vinícius_Contessoto-Final.pdf: 17297320 bytes, checksum: f601c338b5bf6436dc595bad581418f5 (MD5) / Approved for entry into archive by Juliano Benedito Ferreira (julianoferreira@reitoria.unesp.br) on 2016-09-13T13:26:05Z (GMT) No. of bitstreams: 1 contessoto_vg_dr_sjrp.pdf: 17297320 bytes, checksum: f601c338b5bf6436dc595bad581418f5 (MD5) / Made available in DSpace on 2016-09-13T13:26:05Z (GMT). No. of bitstreams: 1 contessoto_vg_dr_sjrp.pdf: 17297320 bytes, checksum: f601c338b5bf6436dc595bad581418f5 (MD5) Previous issue date: 2016-08-16 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Entender a contribuição das interações eletrostáticas no processo de enovelamento e na estabilidade do estado nativo de proteínas é de grande relevância em biofísica molecular. Este trabalho possui duas frentes de estudos. Na primeira etapa é apresentado o estudo das interações eletrostáticas no processo de enovelamento utilizando modelos baseados em estruturas com cargas em dinâmica molecular com pH constante. O estudo foi realizado na parte N-terminal da proteína ribossomal L9 (NTL9), uma proteína com o mecanismo de enovelamento de 2 estados, reversível e realizado desde pH 1.0 até 12.0. Foi possível comparar os resultados das simulações com os resultados experimentais presentes na literatura e os dados obtidos indicam que o modelo proposto é capaz de capturar informações fundamentais sobre o processo de enovelamento referentes à estabilidade e dependência com pH. Na segunda etapa é apresentado o estudo sobre as interações eletrostáticas na estabilidade de enzimas com interesse na produção de bioetanol de segunda geração. O objetivo final deste trabalho é adequar as enzimas às condições do reator para a produção de bioetanol. Neste trabalho foi utilizada uma metodologia capaz de indicar possíveis mutações, pela otimização da interação carga–carga na superfície da proteína, que levam ao aumento de termostabilidade. Este trabalho conta com a colaboração do grupo experimental do Laboratório Nacional de Ciência e Tecnologia do Bioetanol (CTBE) que realizam os testes experimentais e as validações das mutações propostas. / The understanding of electrostatic interactions in protein folding process and in native state stability is important to molecular biophysics area. This work has two areas of interest. At first step it is presented the study about electrostatic interactions in the protein folding process using structure-based models in a constant pH molecular dynamics. It was used the N-terminal domain of ribosomal protein L9 (NTL9), which folding mechanism is a two-state pathway, fully reversible and foldable in a pH range from 1.0 to 12.0. The simulation results were compared with experimental results from literature and the obtained data indicates that the proposed model is capable of capturing essential features of folding mechanism about stability and pH dependence. At second step, it is presented the study about electrostatic interactions in stability of enzymes related with second generation bioethanol production. The final goal of this work is to adjust the enzymes to reactor conditions of bioethanol production. It was employed a method that can suggest rational mutation, based on optimization of charge-charge interactions, that leads to thermostability increase. This work can count on the collaboration of an experimental group of Brazilian Bioethanol Science and Technology Laboratory (CTBE) that performs the wet lab tests and validates the suggested mutations.

Doctor of Philosophy / Department of Chemistry / Paul E. Smith / In the study of biological systems, molecular dynamics (MD) simulations have played an important role in providing atomic details for phenomena of interest. The force field used in MD simulations is a critical factor determining the quality of the simulations. Recently, Kirkwood-Buff (KB) theory has been applied to study preferential interactions and to develop a new force field. KB theory provides a path from quantities determined from simulation data to the corresponding thermodynamic data. Here we combine KB theory and molecular simulations to study a variety of intermolecular interactions in solution. First, recent results concerning the formulation and evaluation of preferential interactions in biological systems in terms of KB integrals are presented. In particular, experimental and simulated preferential interactions of a cosolvent with a biomolecule in the presence of water are described. Second, a force field for the computer simulation of aqueous solutions of amides is presented. The force field is designed to reproduce the experimentally observed density and KB integrals for N-methylacetamide (NMA), allowing for an accurate description of the NMA activity. Other properties such as the translational diffusion constant and heat of mixing are also well reproduced. The force field is then extended to include N,N'-dimethylacetamide and acetamide with good success. The models presented here provide a basis for an accurate force field for peptides and proteins. Comparison between the developed KB force fields (KBFF) and existing force fields is performed for amide and glycine and proves that the KBFF approach is competitive. Also, explicit expressions are developed for the chemical potential derivatives, partial molar volumes, and isothermal compressibility of solution mixtures involving four components at finite concentrations using the KB theory of solutions. A general recursion relationship is also provided which can be used to generate the chemical potential derivatives for higher component solutions. Finally, a pairwise preferential interaction model (PPIM), described by KB integrals is developed to quantify and characterize the interactions between functional groups observed in peptides.