Le développement de la Théorie du Calcul Quantique provient de l'idée qu'un ordinateur est avant tout un système physique, de sorte que ce sont les lois de la Nature elles-mêmes qui constituent une limite ultime sur ce qui peut être calculé ou non. L'intérêt pour cette discipline fut stimulé par la découverte par Peter Shor d'un algorithme quantique rapide pour factoriser un nombre, alors qu'actuellement un tel algorithme n'est pas connu en Théorie du Calcul Classique. Un autre résultat important fut la construction par Lov Grover d'un algorithme capable de retrouver un élément dans une base de donnée non-structurée avec un gain de complexité quadratique par rapport à tout algorithme classique. Alors que ces algorithmes quantiques sont exprimés dans le modèle ``standard' du Calcul Quantique, où le registre évolue de manière discrète dans le temps sous l'application successive de portes quantiques, un nouveau type d'algorithme a été récemment introduit, où le registre évolue continûment dans le temps sous l'action d'un Hamiltonien. Ainsi, l'idée à la base du Calcul Quantique Adiabatique, proposée par Edward Farhi et ses collaborateurs, est d'utiliser un outil traditionnel de la Mécanique Quantique, à savoir le Théorème Adiabatique, pour concevoir des algorithmes quantiques où le registre évolue sous l'influence d'un Hamiltonien variant très lentement, assurant une évolution adiabatique du système. Dans cette thèse, nous montrons tout d'abord comment reproduire le gain quadratique de l'algorithme de Grover au moyen d'un algorithme quantique adiabatique. Ensuite, nous montrons qu'il est possible de traduire ce nouvel algorithme adiabatique, ainsi qu'un autre algorithme de recherche à évolution Hamiltonienne, dans le formalisme des circuits quantiques, de sorte que l'on obtient ainsi trois algorithmes quantiques de recherche très proches dans leur principe. Par la suite, nous utilisons ces résultats pour construire un algorithme adiabatique pour résoudre des problèmes avec structure, utilisant une technique, dite de ``nesting', développée auparavant dans le cadre d'algorithmes quantiques de type circuit. Enfin, nous analysons la résistance au bruit de ces algorithmes adiabatiques, en introduisant un modèle de bruit utilisant la théorie des matrices aléatoires et en étudiant son effet par la théorie des perturbations. / Doctorat en sciences appliquées / info:eu-repo/semantics/nonPublished

Title: Quantum mechanical study of the electron hoping processes of pig- ments from photosystems. Simulation of absorption and emission photoelectron spectra. Author: Bc. Radim Cajzl Department: Department of Chemical Physics and Optics Supervisor: prof. RNDr. Ing. Jaroslav Burda, DrSc., Department of Chemical Physics and Optics Abstract: The aim of this thesis is to develop a methodology for simulation of dynamical properties of carotenoids by OMx method combined with surface electron hopping. We use linear conjugated polyenes: ethene, butadiene, hexa- triene up to polyenes with 22 carbon atoms as model systems. First, the spectra are calculated with sufficiently good agreement with the experimental data by both correct order of excited states and small deviation from experimental data. These results are used for electron surface hopping for calculation of mean lifetimes of excited states of studied polyenes. Calculated lifetimes are of the same order as experimental data for butadiene, hexatriene and octatetraene. Calculated lifetimes for poleynes with 20 resp. 22 carbon atoms agree well with chemically analogous carotenoids. Keywords: quantum mechanics, photoelectron spectra, pigments of photosys- tems, elecrton transitions, molecular and electronic dynamics

I defend three general claims concerning inter-theoretic reduction in physics. First, the popular notion that a superseded theory in physics is generally a simple limit of the theory that supersedes it paints an oversimplified picture of reductive relations in physics. Second, where reduction specifically between two dynamical systems models of a single system is concerned, reduction requires the existence of a particular sort of function from the state space of the low-level (purportedly more accurate and encompassing) model to that of the high-level (purportedly less accurate and encompassing) model that approximately commutes, in a specific sense, with the rules of dynamical evolution prescribed by the models. The third point addresses a tension between, on the one hand, the frequent need to take into account system-specific details in providing a full derivation of the high-level theory’s success in a particular context, and, on the other hand, a desire to understand the general mechanisms and results that under- write reduction between two theories across a wide and disparate range of different systems; I suggest a reconciliation based on the use of partial proofs of reduction, designed to reveal these general mechanisms of reduction at work across a range of systems, while leaving certain gaps to be filled in on the basis of system-specific details. After discussing these points of general methodology, I go on to demonstrate their application to a number of particular inter-theory reductions in physics involving quantum theory. I consider three reductions: first, connecting classical mechanics and non-relativistic quantum mechanics; second,connecting classical electrodynamics and quantum electrodynamics; and third, connecting non-relativistic quantum mechanics and quantum electrodynamics. I approach these reductions from a realist perspective, and for this reason consider two realist interpretations of quantum theory - the Everett and Bohm theories - as potential bases for these reductions. Nevertheless, many of the technical results concerning these reductions pertain also more generally to the bare, uninterpreted formalism of quantum theory. Throughout my analysis, I make the application of the general methodological claims of the thesis explicit, so as to provide concrete illustration of their validity.

This project aims to study general relativity to the extent to understand the occurrence and behaviors of closed timelike curves (CTCs) in several exact solutions of Einstein’s field equations. The rotating black hole solution, the Gödel universe and the cosmic string solutions are studied in detail to show how CTCs arise in these spacetimes. The chronology-violationing paradoxes and other unphysical aspects of CTCs are discussed. The spacetimes where CTCs arise possess properties which are argumented to be unphysical, such as lack of asymptotic flatness and being innite models. With quantum computational networks it is possible to resolve the paradoxes which CTCs evoke. With all these attempts of resolving CTCs, our conclusion is that CTCs exist quantum mechanically, but there is a mechanism which inhibits them to be detected classically. / Detta projekt åsyftar att studera allmän relativitet i den grad att kunna förstå uppkomsten och företeelsen av tidsliknande slutna kurvor (CTC) i några exakta lösningar till Einsteins ekvationer. Dessa lösningar inkluderar Gödel universen, kosmiska strängar och det roterande svarta hålet, där CTC studeras i mer detalj. CTC är kronologi-kränkande företeelser och paradoxen som uppstår presenteras, samt de argument som ligger till grund till att CTC inte är fysikaliskt verkliga objekt. De tidrum där CTC uppkommer delar gemensamma egenskaper som anses ofysikaliska, som att vara icke asymptotiskt platta tidrum, samt att vara oändliga modeller. Med kvantinformatiska nätverk kan CTC illustreras och de klassiska kronologi-paradoxen kan rättas ut. Slutsatsen är att CTC existerar kvantmekaniskt, men det fnns en mekanism i verkligheten som förhindrar dessa att bli detekterade klassiskt.

This dissertation's purpose is to test the hypothesis that beliefs in the possibility of post-mortem survival can be rationally held within the context of the contemporary scientific and philosophical environment. In terms of criteria of rationality, a basic evidentialism is assumed, such that propositions which are sufficiently supported by the available evidence can be rationally held. With regard to the compatibility with contemporary science and philosophy, it follows as a further criterion that the relevant evidence must be satisfactorily anchored within the framework of these traditions. The relevant evidence concerns two levels. First, the basic level of the conceptual coherence of afterlife beliefs is addressed, so that the logical possibility of post-mortem survival can be established. Secondly, the viability of the metaphysics which are implied in the support of the logical possibility (i.e. the metaphysics needed to actualize post-mortem survival) is defended, establishing the metaphysical possibility of post-mortem survival. At this stage, reductive physicalism, which is the only position that effectively undermines post-mortem survival, is criticized, and the problem of interaction which burdens several of the survival-enabling ontologies is addressed. As for the criterion of scientific compatibility, it is further shown that contemporary physics are compatible with the survival-enabling metaphysics, and that contemporary physics can be argued to provide a moderate positive relevance with regard to these positions. The conclusion drawn is that belief in the possibility of post-mortem survival is not only rationally permissible within the framework of contemporary science and philosophy, but also rationally obligatory, i.e. that this possibility cannot rationally be denied with regard to the reviewed evidence.

Residual dipolar couplings can be used to increase the number of qubits for quantum information processing. We have used molecules containing 3, 5 and 8 spins oriented in a liquid crystal matrix, and exploited the residual dipolar coupling to demonstrate quantum information processing in them. Transition assignment is performed using HET-Z-COSY experiment and qubit addressability is achieved by transition selective pulses. It is expected that using this protocol higher qubits can be achieved. For the implementations reported in this work, evolution under the internal Hamiltonian was not explored. It is however interesting to investigate how effectively the evolution under internal Hamiltonian can be manipulated to implement quantum algorithms in these systems. Recently an approach has been reported in this direction, where a new method of preparing pseudopure states in oriented systems by exciting selected multiple quantum using evolution under effective dipolar Hamiltonian, has been demonstrated [24].

We have investigated the noncovalent interactions in carbohydrate-aromatic interactions which are pivotal to the recognition of carbohydrates in proteins. We have employed quantum mechanical methods to study carbohydrate-aromatic complexes. Due to the importance of dispersion contribution to the interaction energy, we mainly use density functional theory augmented with an empirical correction for the dispersion interactions (DFT-D). We have validated this method with a limited number of high level ab initio calculations. We have also analysed the vibrational and NMR chemical shift characteristics using the DFT-D method. We have mainly studied the complexes involving β-glucose with 3-methylindole and p-hydroxytoluene, which are analogues of tryptophan and tyrosine, respectively. We find that the contribution for interaction energy mainly comes from CH/π and OH/π interactions. We find that the interaction energy of complexes involving CH/π and OH/π interactions is reflected in the associated blue and red shifts of vibrational spectrum. We also find that the interactions involving 3-methylindole are somewhat greater than those for p-hydroxytoluene. The C-H blueshifts are also in parallel with the predicted NMR proton shift. We have also tested different density functionals including both standard density functionals and newly developed M0x functionals and MP2 method for studying carbohydrate-aromatic complexes. The DFT-D method and M06 functionals of the M0x family are found to perform better, while B3LYP and BLYP functionals perform poorly. We find that the inclusion of a dispersion term to BLYP is found to perform better. The dispersion energy dominates over the interaction energy of carbohydrate-aromatic complexes. From the DFT-D calculations, we found that the complexes would be unstable without the contribution from dispersive energy. We have also studied the importance of noncovalent interactions in functionalization of nanotubes by nucleic acid bases and aromatic amino acids by using semi-empirical methods with dispersion term such asPM3-D and PM3-D*. We find that the both semi-empirical schemes give reasonable interaction energies with respect to DFT-D interaction energies. We have also used PM3-D method to study the adsorption of organic pollutants on graphene sheet and on nanotubes. We found that the semi-empirical schemes, which are faster and cheaper, are suitable to study these larger molecules involving noncovalent interactions and can be used as an alternative to DFT-D method. We have also studied the importance of dispersion interaction and the effect of steric hindrance in aggregation of functionalized anthracenes and pentacenes. We have also employed molecular dynamics simulation methods to study the aggregation of anthracene molecules in toluene solution.

Noncovalent interactions are of great importance in studies on crystal design and drug discovery. One such noncovalent interaction, halogen bonding, is present between a covalently bound halogen atom and a Lewis base. A halogen bond is a directional interaction caused by the anisotropic distribution of charge on a halogen atom X covalently bound to A, which in turn forms a positive region called σ-hole on the A–X axis. Utilization of halogen bonds in lead optimization have been rarely considered in drug discovery until recently and yet more than 50% of the drug candidates are halogenated. To date, the halogen bond has not been subjected to practical molecular mechanical-molecular dynamics (MM-MD) study, where this noncovalent interaction cannot be described by conventional force fields because they do not account for the anisotropic distribution of the charge density on the halogen atoms. This problem was solved by the author and, for the first time, an extra-point of positive charge was used to represent the σ-hole on the halogen atom. This approach is called positive extra-point (PEP) approach. Interestingly, it was found that the performance of the PEP approach in describing halogen bond was better than the semiempirical methods including the recent halogen-bond corrected PM6 (PM6-DH2X) method. The PEP approach also gave promising results in describing other noncovalent halogen interactions, such as C–X···H and C–X···π-systems. The PEP resulted in an improvement in the accuracy of the electrostatic-potential derived charges of halogen-containing molecules, giving in turn better dipole moments and solvation free energies compared to high-level quantum mechanical and experimental data.With the aid of our PEP approach, the first MM-molecular dynamics (MM-MD) study of inhibitors that form a halogen bond with a receptor was performed for tetrahalobenzotriazole inhibitors complexed to cyclin-dependent protein kinase (CDK2). When the PEP approach was used, the calculated MM-generalized Born surface area (MM-GBSA)//MM-MD binding energies for halobenzimidazole and halobenzotriazole inhibitors complexed with protein kinase CK2 were found to correlate well with the corresponding experimental data, with correlation coefficients R2 of greater than 0.90. The nature and strength of halogen bonding in halo molecule···Lewis base complexes were studied in terms of molecular mechanics using our PEP approach. The contributions of the σ-hole (i.e., positively charged extra-point) and the halogen atom to the strength of this noncovalent interaction were clarified using the atomic parameter contribution to the molecular interaction approach. The molecular mechanical results revealed that the halogen bond is electrostatic and van der Waals in nature. The strength of the halogen bond increases with increasing the magnitude of the extra-point charge. The van der Waals interaction’s contribution to the halogen bond strength is most favorable in chloro complexes, whereas the electrostatic interaction is dominant in iodo complexes.The failure of the PM6 semiempirical method in describing noncovalent halogen interactions —not only halogen bonds, but also hydrogen bonds involving halogen atoms— was reported and corrected by the introduction of a second and third generation of noncovalent halogen interactions correction. The developed correction yielded promising results for the four examined noncovalent halogen interactions, namely: C–X···O, C–X···N, C–X···π-system, and C–X···H interactions.

This thesis contains three main sections. In the first section, we examine methodologies to discriminate Type II protein kinase inhibitors from the Type I inhibitors. We have studied the structure of 55 Type II kinase inhibitors and have notice specific descriptive geometric features. Using this information we have developed a pharmacophore and a shape based screening approach. We have found that these methods did not effectively discriminate between the two inhibitor types used independently, but when combined in a consecutive way – pharmacophore search first, then shape based screening, we have found a method that successfully filtered out all Type I molecules. The effect of protonation states and using different conformer generators were studied as well. This method was then tested on a freely available database of decoy molecules and again shown to be discriminative. In the second section of the thesis, we implement and assess swarm-based docking methods. We implement a repulsive particle swarm optimization (RPSO) based conformational search approach into Autodock 3.05. The performance of this approach with different parameters was then tested on a set of 51 protein ligand complexes. The effect of using different factoring for the cognitive, social and repulsive terms and the importance of the inertia weight were explored. We found that the RPSO method gives similar performance to the particle swarm optimization method. Compared to the genetic algorithm approach used in Autodock 3.05, our RPSO method gives better results in terms of finding lower energy conformations. In the final, third section we have implemented a Monte Carlo (MC) based conformer searching approach into Gaussian03. This enables high level quantum mechanics/molecular mechanics (QM/MM) potentials to be used in docking molecules in a protein active site. This program was tested on two Zn2+ ion-containing complexes, carbonic anhydrase II and cytidine deaminase. The effects of different QM region definitions were explored in both systems. A consecutive and a parallel docking approach were used to study the volume of the active site explored by the MC search algorithm. In case of the carbonic anhydrase II complex, we have used 1,2-difluorobenzene as a ligand to explore the favourable interactions within the binding site. With the cytidine deaminase complex, we have evaluated the ability of the approach to discriminate the native pose from other higher energy conformations during the exploration of the active site of the protein. We find from our initial calculations, that our program is able to perform a conformational search in both cases, and the effect of QM region definition is noticeable, especially in the description of the hydrophobic interactions within the carbonic anhydrase II system. Our approach is also able to find poses of the cytidine deaminase ligand within 1 Å of the native pose.

Orientador: Prof. Dr. Maurício Domingues Coutinho Neto / Coorientador: Prof. Dr. Rodrigo Luiz Oliveira Rodrigues Cunha / Tese (doutorado) - Universidade Federal do ABC, Programa de Pós-Graduação em Ciência e Tecnologia/Química, Santo André, 2018. / Recentemente completaram-se dois séculos da descoberta do selênio, um elemento controverso que pode ser considerado tóxico e ao mesmo tempo essencial. Apesar de suas propriedades antagônicas, compostos de selênio possuem um grande apelo biológico desde o relato de sua incorporação em enzimas, através da selenocisteína. Neste contexto, os compostos de selênio e telúrio tem se destacado devido às suas propriedades anti-inflamatória, antioxidante, antiviral e antimicrobiana. E portanto, como potenciais quimioterápicos contra doenças cardiovasculares, infecciosas, neurológicas e parasitárias. Esses compostos também tem se mostrado promissores na inibição de cisteína-catepsinas. Essas enzimas são ubíquas e participam de diversas funções no organismo humano. Porém, a atividade desregulada de cisteína proteases está relacionada com o desenvolvimento de diversas patologias, que as fazem importantes alvos terapêuticos no planejamento de novos fármacos. Ensaios experimentais com calcogenuranas mostraram bons resultados na inibição de cisteína proteases. Embora o mecanismo de reação desses compostos ainda não tenha sido completamente esclarecido, a literatura propõe que a inibição ocorre através da reação de troca de ligante entre o grupo tiol e o átomo de calcogênio em sua forma hipervalente. Nesta abordagem, cálculos de mecânica quântica foram utilizados para a investigação do mecanismo de reação através da análise da energia livre de Gibbs envolvida em trocas de ligantes, utilizando a teoria do funcional de densidade (DFT), com o funcional B3LYP e base 6311-G+(d), considerando efeitos de dispersão e correção de ponto zero. Cálculos híbridos com metodologia quântica acoplada à dinâmica molecular (Quantum Mechanics / Molecular mechanics - QM/MM) foram desenvolvidos para avaliar a energia envolvida na inibição de papaína por selenurana utilizando o software AMBER em interface com o software Orca. Para a dinâmica molecular utilizou-se o campo de força geral do Amber (General Amber Force Field - GAFF) e o modelo de solvatação explícita TIP3P, enquanto que a os cálculos quânticos usaram abordagem semi-empírica com o funcional PM3 e teoria do funcional da densidade com o funcional BLYP e base def2-SV(P) incluindo efeitos de dispersão. Ensaios de docking molecular também foram realizados para determinar uma configuração de atracamento inicial para os cálculos de QM/MM. Os resultados propõem que as reações de troca de ligante ocorrem em duas etapas distintas, dependentes da acidez do meio. As selenuranas dicloradas eliminam cloro, em meio aquoso, e formam espécies tricoordenadas (DMeSeO, DMeOH+, DMeSH+, DMeCl+) que podem interagir com tiolato provinente de cisteína proteases provocando sua inibição em ambientes ácidos, com barreiras de energia muito pequenas (menor que 3 kcal) ou inexistentes. / Recently two centuries of the discovery of selenium have been completed, a controversial element that can be considered toxic and at the same time essential. Despite their antagonistic properties, selenium compounds have a great biological appeal since the report of their incorporation into enzymes, through selenocysteine. In this context, selenium and tellurium compounds have been prominent due to their anti-inflammatory, antioxidant, antiviral and antimicrobial properties. And therefore, as potential chemotherapeutics against cardiovascular, infectious, neurological and parasitic diseases. These compounds have also been shown to be promising in cysteine-cathepsin inhibition. These enzymes are ubiquitous and participate in various functions in the human body. However, the unregulated activity of cysteine proteases is related to the development of several pathologies, which make them important therapeutic targets in the planning of new drugs. Experimental trials with calcogenurans showed good inhibition of cysteine proteases. Although the mechanism of reaction of these compounds has not yet been fully elucidated, the literature proposes that inhibition occurs through the bound between the thiol group and the calcogen atom in its hypervalent form. In this approach, quantum mechanics calculations were used to investigate the reaction mechanism through the Gibbs free energy analysis involved to ligand exchanges reactions, using for this the density functional theory (DFT) with the B3LYP functional and base 6311-G+(d), considering dispersion effects and zero point correction. Hybrid calculations with Quantum Mechanics/Molecular Mechanics (QM/MM) were developed to evaluate the energy involved in the inhibition of papain by selenuran using AMBER software in interface with Orca software. For the molecular dynamics, the general Amber force field (GAFF) and the explicit solvation model TIP3P were used, while the quantum calculations used a semi-empirical approach with the PM3 functional and the DFT with the functional BLYP and base def2-SV (P) including dispersion effects. Molecular docking assays were also performed to determine an initial docking configuration for the QM/MM calculations. The results suggest that the ligand exchange reactions occur in two distinct steps, depending on the acidity of the medium. The dichlorinated selenuranes eliminate chlorine in aqueous medium and form tricoordinated species (DMeSeO, DMeSeOH+, DMeSeSH+, DMeSeCl+) which can interact with thiolate from cysteine proteases causing their inhibition in acid environments, with very small energy barriers (less than 3 kcal) or nonexistent.