Free energy calculations for the transfer of a water molecule from the pure liquid to an interior cavity site in a protein are presented. Three different protein cavities, in bovine pancreatic trypsin inhibitor (BPTI), the I106A mutant of lysozyme, and in the I76A mutant of barnase, represent very different environments for the water molecule, one which is polar, forming four water-protein hydrogen bonds, and two which are more hydrophobic, only forming one or two water-protein hydrogen bonds. The calculations give very different free energies for the different cavities, with only the polar BPTI cavity predicted to be hydrated. The corresponding entropies for the transfer to the interior cavities are calculated as well and show that the transfer to the polar cavity is significantly entropically unfavorable while the transfer to the non-polar cavity is entropically favorable. For all proteins an analysis of the fluctuations in the positions of the protein atoms shows that the addition of a water molecule makes the protein more flexible. This increased flexibility appears to be due to an increase length and weakened strength of protein-protein hydrogen bonds near the cavity. Similar free energy studies are performed on the three proteins at high pressure, 3 kbar. As in the 1 atm studies BPTI is the only protein that should be hydrated at 3 kbar, however the protein free energy changes appear to be not strongly dependent on the number of hydrogen bonds available. Changes in protein structure and flexibility are analyzed in an attempt to more fully understand the changes proteins undergo prior to pressure induced denaturation. These changes can help understand the forces at work in the last stages of protein folding. The role of interior water in this process is also analyzed. Changes to the fluctuating charge algorithm that handles polarizability in molecular dynamics simulations were performed to allow for longer time steps. The fluctuating charge model treats partial charges as variables which are propagated using Lagrangian dynamics. A coordinate transform to normal mode charge variables is applied to the TIP4P-FQ model of water to decrease the coupling between the atomic and charge degrees of freedom.

Orientador: Michael John Brennan / Resumo: Vazamentos em tubulações de água enterradas são considerados um importante problema já que uma grande quantidade de água é desperdiçada entre a planta de tratamento e os consumidores. Para lidar com tal problema, companhias de saneamento utilizam dispostivos para localizar vazamentos nas tubulações. Dispositivos de escuta e correlacionadores de ruídos são os equipamentos mais utilizados em campo pelas companhias de sanemaneto ao redor do mundo. Correlacionadores de ruídos são dispositivos usados na localização de vazamentos em tubulações enterradas através da estimativa do tempo de atraso entre os sinais medidos pelos sensores posicionados em ambos os lados de um suposto vazamento. Uma vez que as companhias de saneamento devem decidir qual tipo de correlacionador é o mais compatível com a sua rede de tubulações, elas devem realizar alguns testes para ajudar em tal decisão e para treinar os funcionários que operam estes dispositivos, os quais devem ser expostos a diferentes condições, tais como tubos de diferentes materiais e geometrias, diferentes tipos de solo, vazamentos com diferentes intensidades, etc. Neste contexto, o principal objetivo desta pesquisa é contribuir com esta necessidade através da elaboração de um dispositivo de bancada capaz de reproduzir as vibrações de um tubo causadas por um vazamento. O dispositivo, chamado de simulador virtual de vazamentos, é composto por um computador, um amplificador de potência com dois canais e dois shakers. Ruídos de vazamento... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Leakage in buried water pipes is an important problem since a large amount of water is wasted between the treatment plant and the consumers. To deal with such a problem, water companies have used some devices to localize leaks in the pipe network. Listening devices and leak noise correlators are the most popular equipment used in the field by the water companies around the world. Leak noise correlators are important devices used to localize leaks in buried pipes by calculating the time delay between the signals measured by the sensors positioned either side of a suspected leak. Since water companies have to decide which leak noise correlator is more suitable for each pipe network, they have to carry out some field tests to assist in this decision and to train the personnel that handles such a device, which ideally must be exposed to different conditions, such as pipes with different materials and geometries, different types of soil, different leak strengths, etc. The main objective of this research project is to contribute with the necessity of the water companies by designing an indoor bench-top device capable to reproduce the pipe vibrations generated by a leak in the field. The device, called virtual pipe test rig, comprises a computer and a dual-channel power amplifier supplying two shakers. In the computer, leak noise is synthesized by using a model of a buried leaking pipe implemented using the software Matlab®. Since the systems, composed by the power amplifiers and th... (Complete abstract click electronic access below) / Mestre