O processo de flotação por ar dissolvido antecedendo a filtração, constitui hoje técnica já consolidada para clarificação de água para abastecimento. Apesar de apresentar elevada eficiência de remoção de partículas em suspensão e das diversas vantagens associadas a sua utilização, ainda existem particularidades deste processo pouco conhecidas. Visando compreender melhor a flotação por ar dissolvido e contribuir para a otimização das unidades existentes e também nos projetos de novas unidades, foram utilizadas técnicas de fluidodinâmica computacional para estudar as condições de escoamento entre água e ar observadas numa unidade piloto de flotação. A flotação foi investigada através de simulações em ambiente de CFD, acoplado a experimentos laboratoriais em instalação piloto de flotação por ar dissolvido. Estes últimos compreenderam a execução de ensaios com traçador para obtenção das curvas de distribuição de tempo de residência na unidade em questão e também por testes com sonda do tipo Micro ADV para levantamento do perfil de velocidades de escoamento no interior da unidade piloto. Os resultados das análises experimentais com sonda Micro ADV indicaram a presença de escoamento estratificado na região superior da zona de separação da unidade piloto. As curvas de distribuição do tempo de residência apontaram para escoamento do tipo pistonado. O tempo de detenção observado nos ensaios foi de 19,29 e 18,66 minutos respectivamente para escoamento somente de água e sem recirculação e escoamento entre água e ar. As simulações em CFD confirmaram a presença de escoamento estratificado na zona de separação e também a presença de uma manta de microbolhas de ar na mesma. Os resultados foram sensíveis ao diâmetro de microbolhas testado, com maior concentração de ar na zona de separação quando testados diâmetros de microbolhas menores que 60 µm. As curvas de distribuição de tempo de residência obtidas nas simulações em CFD foram capazes de representar o escoamento entre água e ar. O tempo de detenção hidráulico simulado foi de 14,24 e 18,90 minutos respectivamente para as mesmas condições experimentais testadas. De uma maneira geral, as simulações em CFD foram capazes de reproduzir as condições de escoamento entre ar e água observadas na unidade piloto de flotação, os resultados computacionais são condizentes com aqueles obtidos nos ensaios experimentais. / The dissolved air flotation process preceding filtration, consist in established technique for clarification of water supply. Despite presenting high suspended particle removal efficiency and the various advantages associated with their use, there are still a few particularities of this process slightly unknown. To better understand the dissolved air flotation and contribute to the optimization of the existing units and also in projects of new units, computational fluid dynamics techniques were used to study the flow conditions between water and air observed in a flotation pilot plant. The flotation process was investigated in CFD environment, coupled to laboratory experiments in dissolved air flotation scale pilot plant. The latter comprised running tests with tracer to obtain the residence time distribution curves in the pilot plant, tests with micro ADV probe were also conducted for raising the flow velocity profile within the unit. The results of micro ADV experimental analyzes indicated the presence of stratified flow in the upper region of the separation zone of the pilot plant. The residence time distribution curves pointed to plug flow. The retention time observed in the experiments were 19,29 and 18,66 minutes, respectively for the flow of water only and without recirculation and flow of water and air. The CFD simulations confirmed the presence of stratified flow in the separation zone and also the presence of a microbubble air blanket therein. The results were sensitive to the diameter of microbubbles tested, with bigger air concentration in the separation zone when tested with microbubbles diameters smaller than 60 micrometers. The residence time distribution curves obtained in CFD simulations were able to represent the water and air flow. The simulated hydraulic retention times obtained were 14,24 and 18,90 minutes, respectively, for the same experimental conditions. In general, the CFD simulations were able to reproduce the flow conditions observed between air and water in the flotation pilot plant, the computational results were consistent to those obtained in the experiments.

[pt] Neste trabalho apresenta-se uma análise dos principais procedimentos desenvolvidos para calcular a tenacidade à fratura sob condições elastoplásticas. São avaliadas as principais medidas de tenacidade, bem como as diferenças, características, fontes de conservadorismo e as principais referências bibliográficas que relatam diferenças nas metodologias de cálculo para prever as cargas de falha em estruturas com defeito. Também são analisados os principais procedimentos de avaliação da Integridade Estrutural de estruturas com defeito (Fitness For Service, FFS). Testes de tenacidade são feitos variando as condições de restrição em torno da trinca (geometria do CP, tamanho inicial de trinca, entalhe lateral). Foram levantadas as curvas JR para todos os CPs testados, e previsões de carga de fratura são feitas segundo os principais procedimentos FFS, e testes são realizados em placas trincadas centralmente com o objetivo de registrar as cargas de falha do defeito, para compará-las com as previsões dos procedimentos FFS e avaliar o conservadorismo de cada um deles. Como outra contribuição ao trabalho, simulações numéricas dos ensaios de tenacidade são desenvolvidas com o objetivos de reproduzir os testes feitos e calibrar os parâmetros de simulação de rasgamento dúctil em estruturas com defeito. / [en] This work presents an analysis of the main procedures developed to calculate fracture toughness under elastoplastic conditions. The main measures of toughness, differences, characteristics, and sources of conservatism are evaluated. Also, the main bibliographies reporting differences in calculation methods to predict failure loads in flawed structures are examined. Lastly, the main assessment procedures of Structural Integrity of structures with flaws (fitness for service, FFS) are also analyzed.Toughness tests are performed varying the constraint conditions near the crack tip (geometry, initial crack size, side grooves). JR curves and fracture load predictions were made according to the principal FFS procedures. Also, experimental tests are performed on centrally cracked plates in order to record the failure loads of the structure, to compare them with the predictions of FFS procedures and to evaluate their conservatism. Other contributions of this work are numerical simulations of toughness tests, developed in order to reproduce the tests and calibrate the simulation parameters of ductile tearing in structures with flaws.

A monoaminoxidase (MAO) é uma enzima importante, que pode atuar como alvo terapêutico. Inibidores da MAO-A apresentam atividade no tratamento de distúrbios de humor, enquanto os inibidores seletivos da MAO-B tem uso, especialmente, no tratamento da Doença de Parkinson. O conhecimento das interações ENZIMA-INIBIDOR é importante no planejamento de fármacos. Nesse contexto, foram realizados estudos das enzimas MAO-A e MAO-B com diferentes ligantes, através da combinação das metodologias de docking, Dinâmica Molecular e Ensemble Docking. Foram escolhidos os ligantes derivados da 1,4-naftoquinona (1,4-NQ), lapachol, menadiona, norlapachol, A2, B2 e C2, os inibidores comerciais clorgilina (MAO-A) e selegilina (MAO-B) e os substratos naturais serotonina (MAO-A) e dopamina (MAO-B). Os resultados do docking mostraram interação de todos os ligantes com algum dos resíduos da "gaiola aromática" (FAD, Tyr407/Tyr444 para MAO-A, Tyr398/Tyr435 para MAO-B), uma importante região catalítica da MAO. Além disso, a seletividade observada experimentalmente da menadiona com a MAO-B também foi observada no docking. Através da DM, foi possível observar algumas diferenças conformacionais entre as estruturas da MAO-A e MAO-B, que podem explicar a seletividade entre as duas isoformas, como por exemplo, distâncias entre resíduos do sítio ativo e ligações de hidrogênio. A partir do Ensemble Docking, foi verificado que a conformação do receptor influencia significativamente o escore das interações ENZIMA+LIGANTE para ligantes volumosos. / Monoamine oxidase (MAO) is an important enzyme that acts as therapeutic target. MAO-A inhibitors show pharmacological activity in the treatment of mood disorders, whereas MAO-B inhibitors are used especially in treatment of Parkinson's Disease. Knowledge of enzyme-inhibitor interactions is important in drug design. Therefore, studies of MAO-A and MAO-B enzymes with different ligands were performed by combining docking, Molecular Dynamics and Ensemble Docking methodologies. Ligands derived from 1,4-naphthoquinone, lapachol, menadione, nor-lapachol, A2, B2, C2, commercial inhibitors clorgyline (MAO-A) and selegiline (MAO-B) and the natural substrates serotonin (MAO-A) and dopamine (MAO-B) were chosen. The docking results shows interactions of all ligands with some residue of the "aromatic cage” (FAD cofactor, Tyr407/Tyr444 for MAO-A and Tyr398/Tyr435 for MAO-B), an important catalytic region of MAO. Furthermore, the experimentally observed selectivity of menadione with MAO-B was also observed by Docking. In Molecular Dynamics results, conformational differences were observed between MAO-A and MAO-B structures, which could explain the selectivity observed between isoforms, e.g. distances between residues of the active site and hydrogen bonds. Ensemble Docking results shows that the conformation of the receptor significantly influence the score of ENZYME+LIGAND interactions for bulky ligands.

Das lineare Chromosom von S.lividans zeichnet sich durch eine hohe Variabilität insbesondere der chromosomalen Endbereiche aus. Hier finden sich unter anderen auch verschiedene Gene, die bisher einzigartig sind. Nach Klonierung der Gene in E.coli wurden die entsprechenden Genprodukte als His-Tag Fusionsproteine überproduziert, aufgereinigt und zur Herstellung von Antikörpern verwendet. Der untersuchte Abschnitt, als Ganzes und in Unterabschnitten, wurde auf einem Hoch Kopien Vektor in S.lividans transformiert. In extra hierfür konstruierten Vektorsystemen erfolgte die Produktion von His-Tag Proteinen in S.lividans. Nach Fusion von potentiellen Promoterbereichen mit dem promoterlosen EGFP-Gen, gelang deren Identifizierung in enhanced green fluorescent protein (EGFP) produzierenden S.lividans Transformanten. Mit Hilfe eines Vektors, der ein Temperatur sensitives Replikon besitzt, wurden Gene durch die Integration eines Hygromycin-Resistenzgenes ersetzt, bzw. als Fusionsgen mit dem EGFP-Gen erstellt. Ein Flavoprotein wurde zur Homogenität gereinigt. Es wurde nachgewiesen, dass in S.lividans pro Monomer ein FAD-Molekül interagiert. Physiologische Studien zeigen, dass die Synthese des chromosomal determinierten Proteins in S.lividans nur erfolgt, wenn dieser Stamm ein Plasmid- oder chromosomal- kodiertes Thiostrepton Resistenzprotein (23S rRNA Methylase) enthält. Es muss geschlussfolgert werden, dass die Methylierung der 23S rRNA die Translation verschiedener mRNAs beeinflusst. Die Synthese dieses Proteins ist des Weiteren abhängig von hohen Konzentrationen an NaCl und KCl im Medium, wie auch die zweier Aldo-Keto Reduktasen. Disruptionsmutanten eines dieser zwei Aldo-Keto Reduktase-Gene zeigen jeweils eine erhöhte und verfrühte Produktion eines rot gefärbten Mycel-assoziierten Antibiotikums (Undecylprodigiosin), während die eines weiteren (Actinorhodin) unbeeinflusst blieb.

Flavin adenine dinucleotide (FAD) is a coenzyme that participates in the redox process of flavoenzymes. Attempts to characterize the catalytic pathways of these enzymes have relied in part on the use of FAD chemical models. The efforts described in this dissertation focus on the chemical model approach to investigate the mechanism of the monoamine oxidase (MAO) catalyzed oxidation of the cyclic tertiary allylamine 1-methyl-4-(2-methyl-1H-pyrrol-2-yl)-1,2,3,6-tetrahydropyridine (TMMP), which is a close analog of the parkinsonian-inducing designer drug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MAO-B catalyzes the conversion of MPTP and its derivatives into active neurotoxins in the brain that subsequently mediate neurogenerative processes that mimic the events leading to idiopathic Parkinson\'s disease. Monoamine oxidase inhibitors are currently used to treat early stages of Parkinson\'s disease. Two FAD chemical models are examined in this project: 5-ethyl-3-methyllumiflavinium perchlorate (5Et3MLF+ClO4-) and 3-methyllumiflavin (3MLF). The flavinium salt 5Et3MLF+ClO4- is an activated form of 3MLF. These FAD chemical models have been used to examine the MAO catalyzed oxidation. MAO-B is expressed in the brain and is known to be involved in the conversion of TMMP into the neurotoxic metabolite 1-methyl-4-phenyl pyridnium (MMP+). MAO-B is responsible for the alpha-carbon oxidation of TMMP to yield 1-methyl-4-(2-methylpyrrol-2-yl)-2,3-dihydropyridinium (DHP+), which then undergoes a second 2-electron oxidation to MMP+. Previous findings demonstrated that 3MLF and 5Et3MLF+ClO4- promoted the oxidation reaction of primary and secondary amines but not tertiary amines. However, the cyclic tertiary allylamine TMMP has not been examined experimentally. Therefore, the alpha-carbon oxidation of TMMP in the presence of the FAD chemical models is reported in this dissertation. The effect of dioxygen and water on the activity of these FAD models is also investigated. / Ph. D.

Résumé : Cette recherche analyse l'impact des technologies numériques sur l'efficacité de l'innovation des formations professionnelles d'ingénieur, des apprentissages et la flexibilité des dispositifs pédagogiques, ainsi que sur la professionnalisation des enseignants tuteurs universitaires. Ceci, au regard des modèles d'organisation managériale et d’usages pédagogiques des TIC. Les résultats de l’axe 1 indiquent que, les dispositifs de Master présentent un modèle d’organisation bi modale hybride qui impacte directement le déséquilibre de répartition des charges entre distance/présence. L’impact indirect sur les actions managériales favorise la flexibilité des dispositifs en termes de gestion des contraintes professionnelles/distance géographique et l’adaptation horaire, l’ouverture aux projets communs, le libre choix des méthodes et outils de communication collaborative médiatisée, accentués par l’émergence de changements de comportement, et une forte dynamique d’esprit d’équipe acceptant les différences constructives. En revanche, il suscite chez l’étudiant l’expression d’un mal-être se traduisant par la nécessité de souplesse structurelle, un besoin de télé laboratoire et plus de travaux pratiques professionnels en présence. L’axe 2 indique un impact direct sur l’usage pédagogique intensif du groupe d’outils incitatifs et interactifs (Emails, chat, forum, simulations, exerciseurs, conception/modèle graphe), et un usage médiocre du groupe (vidéo/visioconférence, audioconférence), l’absence d’usage du groupe (blog, wiki). En outre, il apparaît que le groupe d’outils (chat, forum, simulation, exerciseur) à usage intensif (presque à tous les UE), sont peu efficaces, contrairement aux outils (vidéo/visioconférence, téléconférence) à usage médiocre (rare à l’UE), qui sont plutôt assez efficace. La structuration des forums a un impact significatif sur l’efficacité d’apprentissage. Les forums de type 2 (assez structurés, 3 ≥ fn < 6), présentent une forte intensité de messages référentiels cognitifs et un comportement initia tif et réactif, assez prononcé. A L’inverse, les forums de type 1 (peu structurés, fn < 3), accentuent les messages (relationnels, de régulation) et l’attitude évaluative. Il apparaît dans les dispositifs hybrides, que la performance des étudiants ne dépend pas simplement de l’usage diversifié et intensif d’outils numériques, mais aussi des facteurs d’autodétermination, motivationnels, le sentiment de compétences et la valeur ajoutée des dispositifs. L’axe 3, présente un impact significatif des dispositifs sur le développement professionnel des enseignants/tuteurs, au niveau du changement des pratiques innovantes et de leur sentiment d’engagement. Il ressort que l’engagement dépend plus de l’intention personnelle d’explorer de nouvelles méthodes pédagogiques à distance par le numérique, et non pas aux prescriptions institutionnelles, ou actions managériales, perçues comme des injonctions institutionnelles.Mots-clés : Management et organisation, Technologies numériques, Innovation et formation d’ingénieurs, flexibilité et efficacité des stratégies, impact dispositifs hybrides ou FAD/e-Learning, actes de langage, pratiques pédagogiques innovantes, développement professionnel / This research analyzes the impact of the digital technologies on the efficiency of innovation of the vocational engineer’s trainings, and the flexibility of educational devices in distance learning, as well as on the professionalization of the teacher’s university guardians. This, with regard to the models of managerial organization and educational practices of ICTS(INFORMATION AND COMMUNICATION TECHNOLOGIES).With the glance as of results from the axis 1, it arises that, the organization devices as regard mater degree, offer the model type bimodal hybrid with an imbalance in the burden-sharing with charges activities higher as distance involved than presence. The indirect impact of managerial actions favor the flexibility of devices in terms of managing professionals constraints as regard distance geographical and the hourly adaptation, the opening to the common projects, the free choice of methods and communications tools. It accentuated the emergency of the behavioral changes, and a strong dynamics of team spirit accepting the constructive differences. In addition, from de axis 2 of search, the intensive use of the inciting digital tools and interactive tool is not enough to explain their effectiveness or performance durably in supporting quality and evolution of the device’s training. It makes emerge the difficulty in organizing, illustrating and sharing the graphic figures or symbols, in order to explain reasoning during the exchanges with (chat, audio conference, and forum).The use of simulation devices is less effective, because of the digital divide (cost access and low speed Internet, infrastructures decayed to the point). Furthermore, the level of structuring of the forums has a significant impact on the effectiveness of training. Forums of the type 2 (structured enough, 3 ≥ fn ≤ 6), presents a high intensity of cognitive/métacognitive’s messages, an initiative and reactive behavior. It is the reverse with the forums type 1 (little structured, fn ≤ 2), where the evaluative attitude and messages that are not directly related to learning are increase than others. It also appears that the performance of the students does not depend simply on the intensive use of tool of the digital tools, but of their self-determination, resulting in their feeling of new competences, the sources of motivation and the added-value of the devices to develop itself in company. It arises from axis 3 that the devices significantly impact the professional development of the teachers/tutors, with the changes of practices digital and a strong personal intention to explore new teaching practices remotely, and not of a commitment related to the managerial or institutional regulations, perceived like injunctions.Keys words: Impact of digital technologies, hybrid devices or FAD/e-Learning, training of engineers of LMD system, flexibility and effectiveness’s pedagogic, acts of language and training quality, practices innovating, professional development of trainer. Management and organization

No description available.

This Ph.D. thesis addresses the structure-function relationship of the multimeric oxidoreductase WrbA with the principal aim being the explanation of the unusual kinetics of this enzyme in molecular terms, and thus getting an insight about its physiological role in bacteria. WrbA is a multimeric enzyme with FMN as a co-factor, catalyzing the oxidation of NADH by a two electrons transfer. Structure and function analysis of WrbA places this enzyme between bacterial flavodoxins and eukaryotic oxidoreductases in terms of its evolutionary relationship. The kinetic activity of WrbA was studied under varying conditions such as temperature, pH etc, and its kinetic mechanism was evaluated from parameters KM and Vmax and confirmed by product inhibition pattern experiments. Crystallization and proteolytic experiments also underpin the functional importance of the multimeric nature of WrbA and aid the understanding of the physiological role of this enzyme in molecular terms.

L'objectif de ce travail est la mise en oeuvre de la mécanique de la rupture et d'un modèle d'endommagement afin de vérifier l'intégrité du réservoir cryotechnique d'ARIANE 5 en présence de défauts. Ces derniers sont généralement assimilés à des fissures surfaciques semi-elliptiques. L'approche globale basée sur l'analyse FAD fournit une prédiction trop conservative lorsque cette méthode utilise le facteur d'intensité K et la ténacité KIc. Ce conservatisme peut toutefois être partiellement levé à condition d'introduire la notion d'intégrale J et d'utiliser une ténacité dérivée de la courbe JR - ∆a afin d'autoriser une légère avancée de la fissure dans le cas d'un matériau ductile. Cette courbe JR - ∆a s'obtient à partir d'essais sur des éprouvettes fissurées de différentes géométries (CT, SENT et SCT). L'approche locale de la rupture constitue cependant la seule alternative possible afin de statuer sur l'acceptabilité d'un défaut suffisamment important pour générer une plasticité étendue. Cette approche nécessite alors de décrire précisément les champs de contrainte et déformation en pointe de fissure. Par conséquent il est nécessaire de tenir compte du caractère anisotrope de la plasticité, lié au procédé de laminage, lors de la modélisation du comportement élasto-plastique del'alliage d'aluminium 2219 T87. Dans cette étude un critère phénoménologique est utilisé pour modéliser la plasticité dont l'anisotropie est décrite par différents coefficients. L'optimisation de ces paramètres repose sur la comparaison entre les résultats issus de simulations numériques et ceux obtenus par des essais sur des éprouvettes lisses et entaillées. L'approche local de la rupture repose également sur la compréhension des micromécanismes de rupture. L'alliage d'aluminium 2219 T87 étudié dans le cadre de cette thèse présenteune rupture ductile dont la phase de germination s'effectue sur les inclusions Al2Cu et constitue le mécanisme prépondérant de la rupture. L'endommagement est modélisé par le modèle de Gurson modifié par Needleman et Tvergaard (GTN). L'anisotopie de rupture est simulée par deux lois de germination différentes selon le sens de laminage et le sens transverse. / The purpose of this work is to use fracture mechanics and damage model to assess the structural integrity of the ARIANE 5 tank containing defects. These flaws are usually assumed to be semi-elliptical surface cracks.This situation can be analysed using the FAD (Failure Assessment Diagram) approach. This method is based on the stress intensity factor K and a material fracture toughness (Kmat) which can be the plane strain fracture toughness (KIC) for a conservative prediction. A more realistic prediction is achieved by employing the integral J and a material parameter derived from crack resistance curve JR - ∆a . This curve is obtained by using cracked test samples with different geometries (CT, SENT and SCT). The local approach to fractureis an alternative method to assess failure in particular in the case of large scale plasticity. In this case, the previous method is not able to give accurate predictions. Analyses based on local approach concepts requirean accurate evaluation of strain and stress fields near the crack tip. It is therefore important to take plastic anisotropy into account to model the plastic behavior of the rolled sheets. In this work this is done using amacroscopic phenomenological model. The parameters of this model are determined by minimizing of the difference between the simulation results and the test measurements for smooth and notched tensile test samples. The local approach to fracture is also based on the understanding of the failure micromechanismsof materials. Ductile fracture of metallic materials can be described as a three stage process. The first is void initiation at inclusions, the second is void growth and the third is void coalescence. Nucleation of defectsat Al2Cu inclusions is the main damage mechanism. In this work, the proposed model for ductile fracture is based on the Gurson model modified by Needleman and Tvergaard (GTN). This model is extended to account for fracture anisotropic by considering two nucleation gaussian laws respectively for rolling andtransverse directions.

Abstract Most proteins carry out their functions through interactions with other molecules. Thus, proteins taking part in similar interactions are likely to carry out related functions. One way to determine whether two proteins do take part in similar interactions is by quantifying the likeness of their structures. This work focuses on the development of methods for the comparison of protein-protein and protein-ligand interactions, as well as their application to structure-based classification schemes. A method based on the MultiMer-align (or MM-align) program was developed and used to compare all known dimeric protein complexes. The results of the comparison demonstrates that the method improves over MM-align in a significant number of cases. The data was employed to classify the complexes, resulting in 1,761 different protein-protein interaction types. Through a statistical model, the number of existing protein-protein interaction types in nature was estimated at around 4,000. The model allowed the establishment of a relationship between the number of quaternary families (sequence-based groups of protein-protein complexes) and quaternary folds (structure-based groups). The interactions between proteins and small organic ligands were studied using sequence-independent methodologies. A new method was introduced to test three similarity metrics. The best of these metrics was subsequently employed, together with five other existing methodologies, to conduct an all-to-all comparison of all the known protein-FAD (Flavin-Adenine Dinucleotide) complexes. The results demonstrates that the new methodology captures the best the similarities between complexes in terms of protein-ligand contacts. Based on the all-to-all comparison, the protein-FAD complexes were subsequently separated into 237 groups. In the majority of cases, the classification divided the complexes according to their annotated function. Using a graph-based description of the FAD-binding sites, each group could be further characterized and uniquely described. The study demonstrates that the newly developed methods are superior to the existing ones. The results indicate that both the known protein-protein and the protein-FAD interactions can be classified into a reduced number of types and that in general terms these classifications are consistent with the proteins' functions. / Tiivistelmä Suurin osa proteiinien toiminnasta tapahtuu vuorovaikutuksessa muiden molekyylien kanssa. Proteiinit, jotka osallistuvat samanlaisiin vuorovaikutuksiin todennäköisesti toimivat samalla tavalla. Kahden proteiinin todennäköisyys esiintyä samanlaisissa vuorovaikutustilanteissa voidaan määrittää tutkimalla niiden rakenteellista samankaltaisuutta. Tämä väitöskirjatyö käsittelee proteiini-proteiini- ja proteiini-ligandi -vuorovaikutusten vertailuun käytettyjen menetelmien kehitystä, ja niiden soveltamista rakenteeseen perustuvissa luokittelujärjestelmissä. Tunnettuja dimeerisiä proteiinikomplekseja tutkittiin uudella MultiMer-align-ohjelmaan (MM-align) perustuvalla menetelmällä. Vertailun tulokset osoittavat, että uusi menetelmä suoriutui MM-alignia paremmin merkittävässä osassa tapauksista. Tuloksia käytettiin myös kompleksien luokitteluun, jonka tuloksena oli 1761 erilaista proteiinien välistä vuorovaikutustyyppiä. Luonnossa esiintyvien proteiinien välisten vuorovaikutusten määrän arvioitiin tilastollisen mallin avulla olevan noin 4000. Tilastollisen mallin avulla saatiin vertailtua sekä sekvenssin (”quaternary families”) sekä rakenteen (”quaternary folds”) mukaan ryhmiteltyjen proteiinikompleksien määriä. Proteiinien ja pienien orgaanisten ligandien välisiä vuorovaikutuksia tutkittiin sekvenssistä riippumattomilla menetelmillä. Uudella menetelmällä testattiin kolmea eri samankaltaisuutta mittaavaa metriikkaa. Näistä parasta käytettiin viiden muun tunnetun menetelmän kanssa vertailemaan kaikkia tunnettuja proteiini-FAD (Flavin-Adenine-Dinucleotide, flaviiniadeniinidinukleotidi) -komplekseja. Proteiini-ligandikontaktien osalta uusi menetelmä kuvasi kompleksien samankaltaisuutta muita menetelmiä paremmin. Vertailun tuloksia hyödyntäen proteiini-FAD-kompleksit luokiteltiin edelleen 237 ryhmään. Suurimmassa osassa tapauksista luokittelujärjestelmä oli onnistunut jakamaan kompleksit ryhmiin niiden toiminnallisuuden mukaisesti. Ryhmät voitiin määritellä yksikäsitteisesti kuvaamalla FAD:n sitoutumispaikka graafisesti. Väitöskirjatyö osoittaa, että siinä kehitetyt menetelmät ovat parempia kuin aikaisemmin käytetyt menetelmät. Tulokset osoittavat, että sekä proteiinien väliset että proteiini-FAD -vuorovaikutukset voidaan luokitella rajattuun määrään vuorovaikutustyyppejä ja yleisesti luokittelu on yhtenevä proteiinien toiminnan suhteen.