Un très grand nombre de représentations a été proposé pour modéliser la liaison chimique, mais les structures de Lewis en particulier sont largement utilisées par la communauté des chimistes expérimentateurs. Les méthodes théoriques se développant sur des structures chimiques claires de type Lewis sont essentiellement utilisées pour la description des états fondamentaux. Par ailleurs, la majorité des chimistes théoriciens utilise des orbitales moléculaires pour décrire les état excités, et manque ainsi de lisibilité. Les états excités sont difficiles à prédire, il convient donc d’utiliser un langage simple pour aboutir à une compréhension commune de ces états. Nous proposons dans cette thèse deux méthodes afin d'accéder aux états excités décrits sur des structures facilement lisibles. D’abord, une méthode de projection permettant de développer un état excité en structure chimique claire de type VB. Cette méthode est rapide car elle ne diagonalise pas d’Hamiltonien VB et elle calcule un taux de confiance servant de garde-fou pour juger la fiabilité de la description de l’état excité. Ensuite, une méthode itérative utilisant un Hamiltonien Super-IC optimise des orbitales VB pour un état excité. Cette méthode couplée à la méthode de projection ouvre un passage vers une compréhension simple des états excités. / A large number of chemical representations has been proposed to model the chemical bond, but in particular Lewis structures are widely used by the experimenters community. The theoretical methods on developing the clear chemical Lewis structures are mainly used for the description of the ground states. Moreover, the majority of theoretical chemists uses molecular orbitals to describe the excited states, and thus lacks clarity. The excited states are difficult to predict, it is appropriate to use simple language to reach a common understanding of these states. We propose in this thesis two methods to access the excited states described on easily readable structures. First, a projection method developing an excited state in clear chemical structure type VB. This method is fast because it does not VB Hamiltonian diagonalizes and calculates a trust factor for a safeguard to judge the description of the excited state. Then an iterative method using a Super-CI Hamiltonian to optimize VB orbitals to an excited state. This method coupled with the projection method opens a way to a simple understanding of the excited states.

<p>Peptide bond formation and translational termination on the ribosome have been simulated by molecular mechanics, free energy perturbation, empirical valence bond (MD/FEP/EVB) and automated docking methods. Recent X-ray crystallographic data is used here to calculate the entire free energy surface for the system complete with substrates, ribosomal groups, solvent molecules and ions. A reaction mechanism for peptide bond formation emerges that is found to be catalyzed by the ribosome, in agreement with kinetic data and activation entropy measurements. The results show a water mediated network of hydrogen bonds, capable of reducing the reorganization energy during peptidyl transfer. The predicted hydrogen bonds and the structure of the active site were later confirmed by new X-ray structures with proper transition states analogs. </p><p>Elongation termination on the ribosome is triggered by binding of a release factor (RF) protein followed by rapid release of the nascent peptide. The structure of the RF, bound to the ribosomal peptidyl transfer center (PTC), has not been resolved in atomic detail. Nor is the mechanism known, by which the hydrolysis proceeds. Using automated docking of a hepta-peptide RF fragment, containing the highly conserved GGQ motif, we identified a conformation capable of catalyzing peptide hydrolysis. The MD/FEP/EVB calculations also reproduce the slow spontaneous release when RF is absent, and rationalize available mutational data. The network of hydrogen bonds, the active site structure, and the reaction mechanism are found to be very similar for both peptidyl transfer and termination. </p><p>New structural data, placing a ribosomal protein (L27) in the PTC, motivated additional MD/FEP/EVB simulations to determine the effect of this protein on peptidyl transfer. The simulations predict that the protein N terminus interacts with the A-site substrate in a way that promotes binding. The catalytic effect of L27 in the ribosome, however, is shown to be marginal and it therefore seems valid to view the PTC as a ribozyme. Simulations with the model substrate puromycin (Pmn) predicts that protonation of the N terminus can reduce the rate of peptidyl transfer. This could explain the different pH-rate profiles measured for Pmn, compared to other substrates.</p>

Peptide bond formation and translational termination on the ribosome have been simulated by molecular mechanics, free energy perturbation, empirical valence bond (MD/FEP/EVB) and automated docking methods. Recent X-ray crystallographic data is used here to calculate the entire free energy surface for the system complete with substrates, ribosomal groups, solvent molecules and ions. A reaction mechanism for peptide bond formation emerges that is found to be catalyzed by the ribosome, in agreement with kinetic data and activation entropy measurements. The results show a water mediated network of hydrogen bonds, capable of reducing the reorganization energy during peptidyl transfer. The predicted hydrogen bonds and the structure of the active site were later confirmed by new X-ray structures with proper transition states analogs. Elongation termination on the ribosome is triggered by binding of a release factor (RF) protein followed by rapid release of the nascent peptide. The structure of the RF, bound to the ribosomal peptidyl transfer center (PTC), has not been resolved in atomic detail. Nor is the mechanism known, by which the hydrolysis proceeds. Using automated docking of a hepta-peptide RF fragment, containing the highly conserved GGQ motif, we identified a conformation capable of catalyzing peptide hydrolysis. The MD/FEP/EVB calculations also reproduce the slow spontaneous release when RF is absent, and rationalize available mutational data. The network of hydrogen bonds, the active site structure, and the reaction mechanism are found to be very similar for both peptidyl transfer and termination. New structural data, placing a ribosomal protein (L27) in the PTC, motivated additional MD/FEP/EVB simulations to determine the effect of this protein on peptidyl transfer. The simulations predict that the protein N terminus interacts with the A-site substrate in a way that promotes binding. The catalytic effect of L27 in the ribosome, however, is shown to be marginal and it therefore seems valid to view the PTC as a ribozyme. Simulations with the model substrate puromycin (Pmn) predicts that protonation of the N terminus can reduce the rate of peptidyl transfer. This could explain the different pH-rate profiles measured for Pmn, compared to other substrates.

No description available.

Phosphoryl transfers are essential chemical reactions in key life processes, including energy production, signal transduction and protein synthesis. They are known for having extremely low reaction rates in aqueous solution, reaching the scale of millions of years. In order to make life possible, enzymes that catalyse phosphoryl transfer, phosphoryl transferases, have evolved to be tremendously proficient catalysts, increasing reaction rates to the millisecond timescale. Due to the nature of the electronic structure of phosphorus atoms, understanding how hydrolysis of phosphate esters occurs is a complex task. Experimental studies on the hydrolysis of phosphate monoesters with acidic leaving groups suggest a concerted mechanism with a loose, metaphosphate-like transition state. Theoretical studies have suggested two possible concerted pathways, either with loose or tight transition state geometries, plus the possibility of a stepwise mechanism with the formation of a phosphorane intermediate. Different pathways were shown to be energetically preferable depending on the acidity of the leaving group. Here we performed computational studies to revisit how this mechanistic shift occurs along a series of aryl phosphate monoesters, suggesting possible factors leading to such change. The fact that distinct pathways can occur in solution could mean that the same is possible for an enzyme active site. We performed simulations on the catalytic activity of β-phosphoglucomutase, suggesting that it is possible for two mechanisms to occur at the same time for the phosphoryl transfer. Curiously, several phosphoryl transferases were shown to be able to catalyse not only phosphate ester hydrolysis, but also the cleavage of other compounds. We modeled the catalytic mechanism of two highly promiscuous members of the alkaline phosphatase superfamily. Our model reproduces key experimental observables and shows that these enzymes are electrostatically flexible, employing the same set of residues to enhance the rates of different reactions, with different electrostatic contributions per residue.

Recent years have seen tremendous developments in methods for computational modeling of (bio-) molecular systems. Ever larger reactive systems are being studied with high accuracy approaches, and high-level QM/MM calculations are being routinely performed. However, applying high-accuracy methods to large biological systems is computationally expensive and becomes problematic when conformational sampling is needed. To address this challenge, classical force field based approaches such as free energy perturbation (FEP) and empirical valence bond calculations (EVB) have been employed in this work. Specifically: Force-field independent metal parameters have been developed for a range of alkaline earth and transition metal ions, which successfully reproduce experimental solvation free energies, metal-oxygen distances, and coordination numbers. These are valuable for the computational study of biological systems. Experimental studies have shown that the epoxide hydrolase from Solanum tuberosum (StEH1) is not only an enantioselective enzyme, but for smaller substrates, displays enantioconvergent behavior. For StEH1, two detailed studies, involving combined experimental and computational efforts have been performed: We first used trans-stilbene oxide to establish the basic reaction mechanism of this enzyme. Importantly, a highly conserved and earlier ignored histidine was identified to be important for catalysis. Following from this, EVB and experiment have been used to investigate the enantioconvergence of the StEH1-catalyzed hydrolysis of styrene oxide. This combined approach involved wildtype StEH1 and an engineered enzyme variant, and established a molecular understanding of enantioconvergent behavior of StEH1. A novel framework was developed for the Computer-Aided Directed Evolution of Enzymes (CADEE), in order to be able to quickly prepare, simulate, and analyze hundreds of enzyme variants. CADEE’s easy applicability is demonstrated in the form of an educational example. In conclusion, classical approaches are a computationally economical means to achieve extensive conformational sampling. Using the EVB approach has enabled me to obtain a molecular understanding of complex enzymatic systems. I have also increased the reach of the EVB approach, through the implementation of CADEE, which enables efficient and highly parallel in silico testing of hundreds-to-thousands of individual enzyme variants.

Thesis advisor: Ziqiang Wang / One of the most unconventional electronic states in high transition temperature cuprate superconductors is the pseudogap state. In the temperature versus doping phase diagram, the pseudogap state straddles across the antiferromagnetic (AF) state near half filling and the superconducting (SC) dome on the hole doped side above the transition temperature Tc. The relationship between the pseudogap state and these two well known states - the AF state and the SC state is believed to be very important for understanding superconductivity and the emergent quantum electronic matter in doped Mott insulators. The pseudogap is characterized by the emergence of a soft gap in the single-particle excitation spectrum in the normal state in the temperature range between Tc and a characteristic temperature T*, i.e. Tc < T < T*. The most puzzling feature of the pseudogap is the nodal-antinodal dichotomy. Observed by ARPES in momentum space, the Fermi surface is gapped out in the antinodal region leaving a Fermi arc of gapless excitations near the nodes. Whether the pseudogap is an incoherent superconducting gap (onegap scenario) or it is a different gap governed by other mechanisms, other than superconductivity, (two-gap scenario) is still under debate. In this thesis I study the particle-particle channel and the particle-hole channel of the valence bond fluctuations away from half filling. Based on a strong-coupling analysis of the t-J model, I argue that the superexchange interaction J induced incommensurate bond centered density wave order is the driving mechanism for the pseudogap state. Low energy density of states (DOS) are eliminated by multiple incommensurate scatterings in the antinodal region at the Fermi level. I show that the interplay between the incommensurate bond centered d-wave density wave instability and the intrinsic electronic inhomogeneity in real cuprate materials is responsible for the observed pseudogap phenomena. Utilizing the spatially unrestricted Gutzwiller approximation, I show that the off-stoichiometric doping induced electrostatic disorder pins the low-energy d-wave bond density fluctuations, resulting in a VBG phase. The antinodal Fermi surface (FS) sections are gapped out, giving rise to a genuine normal state Fermi arc. The length of the Fermi arc shrinks with underdoping below the temperature T* determined by thermal filling of the antinodal pseudogap. Below Tc, the d-wave superconducting gap due to singlet pairing coexists and competes with the VBG pseudogap. The spatial, momentum, temperature and doping dependence of these two gaps are consistent with recent ARPES and STM observations in underdoped and chemically substituted cuprates. The temperature versus doping phase diagram captures the salient properties of the pseudogap phenomena and provides theoretical support for the two-gap scenario. In addition to resolving the complexities of the quantum electronic states in hole-doped cuprates, my unified theory elucidates the important role of the interplay between the strong electronic correlation and the intrinsic electronic disorder in doped transition metal oxides. / Thesis (PhD) — Boston College, 2011. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Physics.

Nesta dissertação estudamos sistemas de spins em redes de baixa dimensionalidade e em temperatura nula, analisando suas transições de fases quânticas. Mais precisamente, estu- damos as propriedades do estado fundamental e as possíveis transições de fase do modelo de Heisenberg quântico antiferromagnético de spin-1/2, com interações entre os primeiros e segundos vizinhos, em diversas redes, e em particular na rede triangular, que é o foco de nosso estudo. Para a obtenção do estado fundamental aproximado, usamos um método variacional em que a rede é particionada num conjunto de plaquetas de sítios. O estado fundamental é escrito como um produto tensorial dos estados das plaquetas. Para a rede triangular, escolhemos um triângulo como uma plaqueta. Quatro fases foram encontra- das: a fase antiferromagnética de Néel, a colinear, a fase de Néel modificada e aquela que denominamos de ligação covalente ressonante. Obtivemos as energias e as magnetizações de subrede em função da razão entre as interações de primeiros e segundos vizinhos. En- tre as fases de Néel e a colinear, podemos observar a fase de ligação covalente ressonante caracterizada como um singleto quanto ao spin de cada plaqueta. / In this thesis we study spin systems in low-dimensional lattices at zero temperature, analyzing their quantum phase transitions. More precisely, we study the properties of the ground state and the possible phase transitions in the antiferromagnetic spin-1/2 quan- tum Heisenberg model with interaction between the first and second neighbors, in several lattices, and in particular in the triangular lattice, which is the focus of our study. To obtain the approximate ground state, we use a variational method in which the lattice is partitioned into a set of plates of sites. The ground state is written as a tensor product of the states of plates. For the triangular lattice, we choose a triangle as a plate. Four phases were found: the antiferromagnetic Néel phase, the collinear, the modified Néel phase and that we call resonating valence bond. We obtained the energy and the magnetization as a function of the ratio of the interactions between the first and second neighbor sites. Between the Néel and collinear phases, we can observe the spin resonating valence bond phase, characterized as a singlet with respect to the spin of each plate.

Nesta dissertação estudamos sistemas de spins em redes de baixa dimensionalidade e em temperatura nula, analisando suas transições de fases quânticas. Mais precisamente, estu- damos as propriedades do estado fundamental e as possíveis transições de fase do modelo de Heisenberg quântico antiferromagnético de spin-1/2, com interações entre os primeiros e segundos vizinhos, em diversas redes, e em particular na rede triangular, que é o foco de nosso estudo. Para a obtenção do estado fundamental aproximado, usamos um método variacional em que a rede é particionada num conjunto de plaquetas de sítios. O estado fundamental é escrito como um produto tensorial dos estados das plaquetas. Para a rede triangular, escolhemos um triângulo como uma plaqueta. Quatro fases foram encontra- das: a fase antiferromagnética de Néel, a colinear, a fase de Néel modificada e aquela que denominamos de ligação covalente ressonante. Obtivemos as energias e as magnetizações de subrede em função da razão entre as interações de primeiros e segundos vizinhos. En- tre as fases de Néel e a colinear, podemos observar a fase de ligação covalente ressonante caracterizada como um singleto quanto ao spin de cada plaqueta. / In this thesis we study spin systems in low-dimensional lattices at zero temperature, analyzing their quantum phase transitions. More precisely, we study the properties of the ground state and the possible phase transitions in the antiferromagnetic spin-1/2 quan- tum Heisenberg model with interaction between the first and second neighbors, in several lattices, and in particular in the triangular lattice, which is the focus of our study. To obtain the approximate ground state, we use a variational method in which the lattice is partitioned into a set of plates of sites. The ground state is written as a tensor product of the states of plates. For the triangular lattice, we choose a triangle as a plate. Four phases were found: the antiferromagnetic Néel phase, the collinear, the modified Néel phase and that we call resonating valence bond. We obtained the energy and the magnetization as a function of the ratio of the interactions between the first and second neighbor sites. Between the Néel and collinear phases, we can observe the spin resonating valence bond phase, characterized as a singlet with respect to the spin of each plate.

Quantum magnetic materials provide pathways to exotic spin-disordered phases. We study two broad classes of quantum spin systems and their ground states. The first class is that of spin-dimer systems, which form valence-bond-solid states. In such systems, competition between interactions among the dimers can lead to interesting magnetization behaviour. We explain the magnetization of Ba3Cr2O8 as a Bose-Einstein condensate of spin-carrying excitations. Furthermore, we investigate possible dimerized and nearby magnetically ordered states in the Shastry-Sutherland compound (CuCl)LaNb2O7. The second class of spin systems feature geometric frustration, which may stabilize spin-liquid states without any order or particular dimerization. We argue the proximity of the face-centred-cubic double perovskite La2LiMoO6 to such a phase, to explain its lack of long-range order. We argue for the coexistence of such a state, along with spiral magnetic order, to explain the anomalous thermodynamic measurements in the spin-density-wave phase of powder samples of Volborthite, a distorted kagome-lattice spin system. Finally, we study spin liquid phases that have spin correlations consistent with those found from inelastic neutron scattering of the disordered kagome-lattice material Herbertsmithite. We predict electron spin resonance absorption lineshapes associated with these phases.