The organization of two or more biological macromolecules into a functioning assembly is critical for many biological functions to occur. This phenomenon is the result of subtle interplay between complimentary structural and electrostatic factors. While a growing protein data bank of solved protein structures provides experimental evidence for studying the structural factors that stabilize protein-protein interface, there has been little advance in experimental determination of the electrostatic contributions. This lack of experimental investigation into protein electrostatics results in an inability to describe or predict how protein-protein complexes are arranged and stabilized. This problem is addressed in this dissertation by use of vibrational Stark effect (VSE) spectroscopy in which the spectral transitions of a vibrational probe are directly related to the strength and direction of the electric fields in the vicinity of the probe. The work presented here details an approach using VSE spectroscopy coupled with molecular dynamics simulation (MD) to interpret the role that electrostatics play in organizing the signaling protein Ras' interactions with its downstream effectors Raf and Ral guanosine dissociation simulator (RalGDS). Each chapter describes a specific set of experiments and MD simulations designed to understand the nature of protein-protein interactions. In Chapter 3, changes in the absorption energy of the nitrile probe at nine positions along the Ras-Ral interface were compared to results of a previous study examining this interface with Ral-based probes, and a pattern of low electrostatic field in the core of the interface surrounded by a ring of high electrostatic field around the perimeter of the interface was found. The areas of conserved Stark shifts are used to help describe electrostatic factors that stabilize the Ras-Ral interface. In Chapter 4, VSE is used to describe an electrostatic origin to the binding tilt between complexes formed between Ras and its two effectors Raf and Ral. There are three regions of conserved Stark effect shifts upon docking with WT Ras between the two effectors, indicating that the docked complexes conserve electrostatic fields, resulting in different binding orientation of otherwise structurally similar proteins. Chapter 5 details the use of MD simulation in correlation with VSE data for 18 mutants of the Ras at the oncogenic position 61 site. The combination of experimental and simulations support the hypothesis that position 61 on Ras is used to coordinate an active site water molecule during native guanosine triphosphate (GTP) hydrolysis. / text

Thesis (Ph. D.)--University of Florida, 1982. / Description based on print version record. Typescript. Vita. Includes bibliographical references (leaves 72-74).

Universiẗat, Diss., 2000--Kiel.

Techn. Universiẗat Diss., 2004--Berlin.

Techn. Universiẗat, Diss., 2005--Berlin.

Abstract The topic of this thesis is superconducting electric circuits. Technical advances have made possible the experimental study of Josephson junction based circuit elements which sustain quantum mechanical properties long enough to be denoted as quantum devices. The quantum state can be controlled with electronic variables and measured using standard electrical setups. The research is motivated by the possibility to examine quantum phenomena in circumstances that can be customized, prospects of new quantum devices, and the development of quantum information processing. This thesis presents theoretical studies on the nonlinear and stochastic driving of a superconducting quantum two-level system (qubit). We first investigate the energy level shifts a single-Cooper-pair transistor under large amplitude driving realized via the inherently nonlinear Josephson energy by using an external magnetic flux. The effective driving field substantially deviates from a circular polarization and linear coupling. The energy level shifts are compared to the cases of a vanishing and a weak driving field, measured as the Stark shift and the generalized Bloch-Siegert shift, respectively. We describe criteria for the natural basis of the analytical and the numerical calculations. In addition to that, we develop a formalism based on the Floquet method for the weak probe measurement of the strongly driven qubit. In the latter part of the thesis research, we study utilization of a stochastic driving field whose time evolution is not regular but follows probabilistic laws. We concentrate on the motional averaging phenomenon and show that it can be measured with an unparalleled accuracy by employing a flux-modulated transmon qubit. As the stochastically modulated qubit is simultaneously measured with a moderate driving field, we develop a theoretical description accounting the possible interference effects between the modulation and the drive. The comparison with experimental results shows good agreement. Motional averaging phenomenon can be applied to estimate the properties of fluctuation processes occurring in qubits, e.g., the quasiparticle tunneling or the photon shot noise. Resting on the motional averaging, we anticipate that the qubit dephasing times can be improved if one can accelerate the dynamics of two-level fluctuators. We apply a semiclassical formalism where the qubit is treated with quantum mechanical concepts whereas the driving fields are classical. In the solution procedure, the numerical results support the main analytical understanding. As the theoretical results are extensively compared to reflection measurements, we construct an explicit connection between the dynamics of the studied quantum devices and the measured reflection coefficient.

In this thesis, we investigate several topics pertaining to emergent collective quantum phenomena in the domain of correlated fermions, using the quantum Monte Carlo method. They display exotic low temperature phases as well as phase transitions which are beyond the Landau–Ginzburg theory. The interplay between three key points is crucial for us: fermion statistics, many body effects and topology. We highlight the following several achievements: 1. Successful modeling of continuum field theories with lattice Hamiltonians, 2. their sign-problem-free Monte Carlo simulations of these models, 3. and numerical results beyond mean field descriptions. First, we consider a model of Dirac fermions with a spin rotational invariant inter- action term that dynamically generates a quantum spin Hall insulator. Surprisingly, an s-wave superconducting phase emerges due to the condensation of topological de- fects of the spin Hall order parameter. When particle-hole symmetry is present, the phase transition between the topological insulator and the superconducting phase is an example of a deconfined quantum critical point(DQCP). Although its low energy effec- tive field theory is purely bosonic, the exact conservation law of the skyrmion number operator rules out the possibility of realizing this critical point in lattice boson models. This work is published in Ref. [1]. Second, we dope the dynamically generated quantum spin Hall insulator mentioned above. Hence it is described by a field theory without Lorentz invariance due to the lack of particle-hole symmetry. This sheds light on the extremely hot topic of twisted bilayergraphene: Why is superconductivity generated when the repulsive Coulomb interaction is much stronger than the electron-phonon coupling energy scale? In our case, Cooper pairs come from the topological skyrmion defects of the spin current order parameter, which are charged. Remarkably, the nature of the phase transition is highly non-mean-field-like: one is not allowed to simply view pairs of electrons as single bosons in a superfluid-Mott insulator transition, since the spin-current order parameter can not be ignored. Again, due to the aforementioned skyrmions, the two order parameters are intertwined: One phase transition occurs between the two symmetry breaking states. This work is summarized in Ref. [2]. Third, we investigate the 2 + 1 dimensional O(5) nonlinear sigma model with a topological Wess-Zumino-Witten term. Remarkably, we are able to perform Monte Carlo calculations with a UV cutoff given by the Dirac Landau level quantization. It is a successful example of simulating a continuous field theory without lattice regularization which leads to an additional symmetry breaking. The Dirac background and the five anti-commuting Dirac mass terms naturally introduce the picture of a non-trivial Berry phase contribution in the parameter space of the five component order parameter. Using the finite size scaling method given by the flux quantization, we find a stable critical phase in the low stiffness region of the sigma model. This is a candidate ground state of DQCP when the O(5) symmetry breaking terms are irrelevant at the critical point. Again, it has a bosonic low energy field theory which is seemingly unable to be realized in pure boson Hamiltonians. This work is summarized in Ref. [3]. / In dieser Arbeit untersuchen wir verschiedene Themen über emergente kollektive Quan- tenphänomene im Bereich der korrelierten Fermionen unter Verwendung der Quanten- Monte-Carlo-Methode. Sie zeigen sowohl exotische Tieftemperaturphasen als auch Phasenübergänge, die jenseits der Landau-Ginzburg-Theorie liegen. Das Zusammen- spiel von drei Schlüsselpunkten ist für uns entscheidend: Fermionenstatistik, Vielteilch- eneffekte und Topologie. Es sind bemerkenswerte Erfolge erzielt worden: 1. Erfolgre- iche Modellierung mehrerer kontinuierlicher Feldtheorien über Gitter-Hamiltonians. 2. Vorzeichenproblem-freie Monte-Carlo-Simulation von ihnen. 3. Numerische Ergebnisse jenseits des Molekularfeld-Verständnisses. Zunächst betrachten wir ein Modell von Dirac-Fermionen mit einem spinrotations- invarianten Wechselwirkungsterm, der dynamisch einen Quanten-Spin-Hall-Zustand erzeugt. Überraschenderweise entsteht eine s-Wellen-supraleitende Phase durch die Kondensation von topologischen Defekten des Spin-Hall-Ordnungsparameters. Wenn Teilchen-Loch-Symmetrie vorhanden ist, ist dieser Phasenübergang zwischen topologis- chem Isolator und Supraleiter ein Beispiel für einen dekondefinierten quantenkritischen Punkt (DQCP). Obwohl seine niedrigenergetische effektive Feldtheorie rein bosonisch ist, schließt der exakte Erhaltungssatz des Skyrmionenzahloperators die Möglichkeit aus, diesen kritischen Punkt in Gitter-Boson-Modellen zu realisieren. Diese Arbeit ist veröffentlicht in Ref. [1]. Zweitens dotieren wir den dynamisch erzeugten Quanten-Spin-Hall-Isolator von oben. Er wird aufgrund der fehlenden Teilchen-Loch-Symmetrie durch eine Feldtheorie ohne Lorenzt-Invarianz beschrieben. Dies wirft ein Licht auf das extrem heiße Thema des verdrehten Doppelschichtgraphens: Warum wird Supraleitung erzeugt, wenn die ab- stoßende Coulombwechselwirkung viel stärker ist als die Elektron-Phonon Kopplungsen- ergie? In unserem Fall kommen Kupferpaare aus den topologischen Skyrmiondefekten der Parameter der Spinstromordnung, die geladen sind. Bemerkenswerterweise ist die Art des Phasenübergangs in hohem Maße nicht molekularfeldartig: Es ist nicht erlaubt, ein Elektronenpaar einfach als einzelnes Boson in einem Superfluid-Mott- Isolator-Übergang zu betrachten, da der Parameter der Spin-Strom-Ordnung nicht ignoriert werden kann. Wiederum aufgrund der oben erwähnten Skyrimionen, sind zwei Ordnungsparameter miteinander verbunden: ein Phasenübergang findet zwischen den beiden Zuständen mit gebrochener Symmetrie statt. Diese Arbeit ist in Ref. [2]. Drittens untersuchten wir das 2 + 1-dimensionale nichtlineare O(5)-Sigma-Modell mit einem topologischen Wess-Zumino-Witten-Term. Bemerkenswerterweise sind wir in der Lage, Monte-Carlo-Berechnungen durchzuführen, mit UV-Cutoff gegeben durch die Quantifizierung der Dirac-Landau-Ebenen. Es ist ein erfolgreiches Beispiel für die Simulation einer kontinuierlichen Feldtheorie ohne Gitterregularisierung, die zu zusätzlichen Symmetriebrechungen führt. Der Dirac-Hintergrund und die 5 antikom- mutiernenden Dirac-Massenterme führen natürlich das Bild eines nicht-trivialen Berryphasen Beitrags im Parameterraum des Ordnungsparameters mit fünf Komponenten ein. Unter Verwendung der Methode der endlichen Größenskalierung, die durch Flussquantisierung gegeben ist, fanden wir eine stabile kritische Phase im Bereich der niedrigen Steifigkeit des Sigma-Modells. Dies ist ein Kandidat für den Grundzustand des DQCP, wenn die O(5)-Symmetrie brechenden Terme am kritischen Punkt irrelevant sind. Auch hier handelt es sich um eine niedrigenergetische bosonische Feldtheorie, die scheinbar durch reine Boson-Hamiltonians nicht realisiert werden kann. Diese Arbeit ist in Ref. [3].

No description available.

No description available.

Repair mechanisms for damaged DNA are essential for the proliferation of nearly all forms of life. Although DNA is quite robust, the vital information-storing molecule can often be damaged from environmental exposures such as ultra-violet (UV) light. Exposure to UV light can result in various types of mutagens creating structural damages. One specific type of UV-induced damage is the creation of a cyclobutylpyrimidine dimer (CPD). This specific type of lesion can be efficiently repaired by the flavoenzyme DNA photolyase (PL). DNA photolyase is an ancient protein found across kingdoms and plays a crucial role in preventing mutagenesis and cell death. DNA photolyase is a monomeric flavoprotein that utilizes blue light to repair UV-induced CPD lesions in DNA via an electron transfer mechanism. All photolyases contain at least one flavin adenine dinucleotide (FAD) molecule as the catalytic cofactor responsible for initiating the electron transfer induced repair process. Flavin cofactors are intriguing because of their unique ability to donate one or two electrons. The conservation of FAD and the unique U-shaped configuration of FAD in PL led researchers to question if the adenine moiety of the FAD molecule was essential in the DNA repair mechanism and generated a spectral signature indicative of a radical adenine species. The importance of the adenine moiety could be linked to structural changes associated with environmental temperature. The rate of electron transfer is exponentially dependent on temperature and DNA photolyase is found in organisms which thrive in harsh environments that vary in temperature, pH, ionic strength etc. Photolyase presents a unique opportunity to study the adaptations that are required for proteins to function in extreme environments where temperature dependent processes should show dramatic differences. We have used ultrafast transient absorption spectroscopy to compare the similarities and differences in excited state dynamics of the FAD cofactor. Photolyase isolated from the hyperthermophilic archaea Sulfolobus solfataricus (SsPL) is compared to PL isolated from the mesophilic E. coli (EcPL). These results indicate differences in the dynamics of fully reduced flavin between enzymes as a function of temperature. We present evidence for charge separation in the FAD cofactor in the thermophilic enzyme previously seen in computation studies of photolyase. To investigate the excited state charge redistribution of flavin which is critical to its role in nature, the charge redistribution of the precursors to flavin biosynthesis were examined. Lumazine is a precursor in the biosynthetic pathway of flavins. As such, lumazine could have served as an enzymatic cofactor prior to flavins. Lumazine has been identified in biological processes, however it is not as prevalent as flavins. We utilize Stark spectroscopy to examine the charge redistribution in excited state lumazine to understand / Chemistry