Molecular dynamics simulations are an increasingly valuable tool to biochemical researchers: advances in computational power have expanded the range of biomolecules that can be simulated, and parameters describing these interactions are increasingly accurate. Despite substantial progress in force field parameterization, recent simulations of protein molecules using state-of-the-art, fixed-charge force fields revealed that the interactions among and within protein molecules can be too favorable, resulting in unrealistic aggregation or structural collapse of the proteins being simulated. To understand why these protein-protein interactions are so over-stabilized, I first assessed the ability of simulation force fields to represent accurately the interactions of individual amino acids, employing an osmotic pressure simulation apparatus that enabled direct comparison with experiment. Surprisingly, simulations of most of the amino acids resulted in behavior that was in strong agreement with experiment. A number of amino acids, however—notably those that contain hydroxyl groups and those that carry a formal charge—interacted in ways that were clearly inaccurate. Additionally, some commonly-used force fields failed to accurately represent the interactions of amino acids in a consistent manner. By further investigating the interactions of the functional groups of these amino acids, I was able not only to determine some of the root causes of individual amino acid inaccuracies, but also to implement simple modifications that brought the interactions of these small molecules and amino acids in stronger accord with experiment. These studies have highlighted some of the shortcomings in popular simulation force fields, and have proposed useful modifications to address them. Still, there is additional work that must be—and is being—conducted in order to correctly model the interaction behavior of proteins in simulation.

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No. of bitstreams: 1 FERREIRA_Larissa_2015.pdf: 46221411 bytes, checksum: ae8a0358ebf5e33024f58e5c75dae037 (MD5) Previous issue date: 2015-11-11 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Some conservation actions require the knowledge of the geographical distribution of species, however, this knowledge is far from being achieved for most species. The species distribution models (SDMs) have proved a useful tool to predict the distribution of species and guide field research to find new records. The SDMs using field data occurrence and environmental variables to indicate potential sites for the occurrence of a species. The quality and quantity of the data used are important to a successful result prediction models and application to conservation. The choice of environmental data and the algorithm and their settings are important for the development of models, the choice of these variables have directly influences to the quality of the models. Another very important step in modeling is the quality assessment and validation of the model, is that it may decrease the risk of accepting as true models with gross errors. The objective of this study is to evaluate the applicability of models generated by MaxEnt to find new populations of plants considering different data configurations used. For this, considering that the field validation is the most appropriate in the literature, but the most costly, the first chapter proposes a validation methodology of the models as easy application field. The methodology was able to find new records in the field, therefore, indicated for the validation of models. In the second chapter, knowing of the existence of a wide variety of variables that influence the performance of the models, the aim was to test the influence of the sample size, the spatial bias, the set of climate data and settings available for the MaxEnt algorithm in the areas of prediction potential distribution. The results demonstrated that the use of sampling and climate data restricted to the limit of the study area and also the use of soil data generate more accurate models. / Algumas ações conservacionistas necessitam do conhecimento da distribuição geográfica das espécies, porém, esse conhecimento está longe de ser alcançado para a maioria das espécies. Os modelos de distribuição de espécies (MDEs) têm se mostrado uma ferramenta útil para prever a distribuição das espécies e guiar pesquisas de campo para encontrar novos registros. Os MDEs utilizam dados de ocorrência e variáveis ambientais para indicar locais potenciais para a ocorrência de uma espécie. A precisão e quantidade dos dados utilizados são importantes para um bom resultado de predição dos modelos e aplicação à conservação. A escolha dos dados ambientais e do algoritmo e suas configurações são essenciais para o desenvolvimento dos modelos, pois influenciam diretamente na qualidade dos mesmos. Outra etapa bastante importante na modelagem é a validação do modelo, pois é ela que diminui o risco de aceitar como verdadeiros modelos que possuem erros grosseiros. O objetivo principal deste estudo é avaliar a aplicabilidade de modelos gerados pelo MaxEnt para encontrar populações de plantas, considerando diferentes configurações dos dados utilizados. Para isso o primeiro capítulo propõe uma metodologia de validação dos modelos em campo de fácil aplicação, uma vez que a validação em campo é a mais indicada pela literatura. A metodologia proposta no capítulo um é uma adaptação ao método de “caminhamento” ou método expedito de levantamento e caracterização da vegetação. A metodologia proposta foi eficaz para a localização das espécies em campo e mostrou que a caracterização da vegetação é uma etapa importante para a interpretação dos resultados, uma vez que explicou a ausência de duas espécies em áreas onde o modelo havia previsto presença. Apresenta como principal desvantagem a necessidade de pessoas experientes para o reconhecimento das espécies de plantas para a sua aplicação de forma agilizada. No segundo capítulo, foi testada a influência da área de amostragem, do conjunto de dados climáticos e das configurações do algoritmo Maxent na predição de áreas potenciais de distribuição. Os resultados obtidos demonstraram que o uso de dados amostrais e climáticos restritos aos limites da área de interesse para a busca das espécies e a inclusão de dados de solo geram modelos mais acurados. Mostrou também que as diferentes configurações do Maxent geraram modelos muito similares.

Conformational dynamics are important to the function of biological molecules. While many experimental techniques (e.g. X-ray crystallography and NMR spectroscopy) have been developed for providing the structure of functional conformations, it is exceptionally challenging to understand conformational dynamics from experimental characterization. Molecular dynamics (MD) simulations is a powerful tool for probing conformational dynamics. The timescale resolution of MD simulations enables people to investigate intermediate conformations and transition pathways in atomic detail. Recent advancements in computer hardware have increased the timescales accessible to MD simulations. Meanwhile, more accurate and specific force fields have been developed to accurately model a variety biological system of different sizes. My graduate research has been focused on using MD simulations to study the conformational dynamics of proteins. Markov State Model (MSM) based approaches are extensively applied to investigate a variety of folding and/or binding mechanisms in atomic detail. Another focus of my work has been developing a Bayesian inference-based approach called BICePs to reconcile experimental measurements with simulation data to determine conformational ensembles and to validate force fields. / Chemistry

In web forms, feedback can be provided to users at different points in time. This study investigates these three ways of providing feedback to find which results in the shortest completion time, which results in the lowest number of gaze revisits to input fields, and which type of feedback the users prefer. This was investigated through development of prototypes that were tested with 30 participants in a within-group design after which they were interviewed about their experiences. Providing feedback instantly or after form submission resulted in significantly shorter completion times than providing feedback after users left a field. Providing feedback instantly also resulted in significantly fewer revisits to input fields compared to providing feedback after leaving a field. Through a thematic analysis, users’ experiences were shown to be the most negative when given feedback after form submission, while the most positive experiences occurred when users were given feedback immediately. The results indicate that providing feedback immediately may be an equally good or better alternative to earlier research recommendations to provide feedback after form submission and that revisits to areas of interest may, with further research, be a measurement of optimal scanpath disruption.

Im Bereich der industriellen Metallurgie und Kristallzüchtung treten bei zahlreichen Anwendungen, wo magnetische Wechselfelder zur induktiven Beeinflussung von leitfähigen Werkstoffen eingesetzt werden, auch Strömungen mit freier Oberfläche auf. Das Anwendungsspektrum reicht dabei vom einfachen Aufschmelzen eines Metalls in einem offenen Tiegel bis hin zur vollständigen Levitation. Auch der sogenannte RGS-Prozess, ein substratbasiertes Kristallisationsverfahren zur Herstellung siliziumbasierter Dünnschichtmaterialien, ist dafür ein Beispiel. Um bei solchen Prozessen die Interaktion von Magnetfeld und Strömung zu untersuchen, ist die numerische Simulationen ein wertvolles Hilfsmittel. Für beliebige dreidimensionale Probleme werden entsprechende Berechnungen bisher durch eine externe Kopplung kommerzieller Programme realisiert, die für Magnetfeld und Strömung jeweils unterschiedliche numerische Techniken nutzen. Diese Vorgehensweise ist jedoch im Allgemeinen mit unnötigem Rechenaufwand verbunden. In dieser Arbeit wird ein neu entwickelter Methodenapparat auf Basis der FVM vorgestellt, mit welchem sich diese Art von Berechnungen effizient durchführen lassen. Mit der Implementierung dieser Methoden in foam-extend, einer erweiterten Version der quelloffenen Software OpenFOAM, ist daraus ein leistungsfähiges Werkzeug in Form einer freien Simulationsplattform entstanden, welches sich durch einen modularen Aufbau leicht erweitern lässt. Mit dieser Plattform wurden in foam-extend auch erstmalig dreidimensionale Induktionsprozesse im Frequenzraum gelöst.