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Acid-sensing ion channels (ASICs) are trimeric, sodium-selective proton-gated ion channels. Having ligands as small as protons presents a challenge when studying the structure-function relationships of pH-dependent gating. Knowing where protons must bind to evoke a pH-dependent conformational change related to gating would provide one with insights into the molecular mechanisms underlying pH-dependent function in ASICs. We use molecular dynamics (MD) simulations that allow us to model explicit protons and directly examine the effects of changing protonation states on ASIC1 dynamics. We first combine the use of unbiased MD simulations with pKₐ prediction on the three functional states of cASIC1 to identify the effects of protonation state changes on interactions between ionizable residues in the acidic pocket (ACP), a region rich in acidic residues in the protein that plays a role in pH-sensing. We interpret the importance of E98, a buried residue in the ACP with a highly shifted pKₐ value, as well as the positively charged R191, also in the ACP, which has a flexible side chain and can interact with multiple negatively charged side chains, and the role of these residues in the pH-dependent collapse of the ACP. Additionally, we identify a hydrogen-bond network in the palm domain that consists of the Q277 side chain that interacts with the E80 side chain and L414 backbone carbonyl. This network contributes to a stable desensitized state and is stabilized by an E80-/E412H/E417H protonation configuration. Next, targeted MD was combined with pKₐ prediction to simulate the full transition pathways and to link protonation states with the molecular mechanisms involved in conformational changes. Our results suggest four residues, E98, E314, H328, and E374, that may be important in pH-sensing and gating, and that require further functional investigation in the context of activation and desensitization. This research exemplifies how MD is a useful tool in studying how protonation directly affects the structural dynamics of a protein and how it can complement existing functional studies and be used to suggest future experimental investigations.

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The construction of a field emission ion source and its adaptation to a mass spectrometer is described. The problems involved and the advantages of such an ion source are discussed. / Thesis / Master of Science (MS)

This thesis investigates low-energy xenon-molybdenum (Xe+-Mo) sputtering yields for ion energies of 100 eV and less. Sputtering yield data at these energies are important for ion thruster design and lifetime prediction. The basic principles of sputtering phenomena are discussed. An overview of various popular types of experimental sputtering yield methods is presented with an emphasis on the techniques that have been used to find Xe+-Mo sputtering yields in the past. Sputtering yields in this study are found through both models and experiments. Sputtering yields are calculated using the Sigmund, Bohdansky, Yamamura, and Wilhelm formulas. The computed sputtering yields for these models varied widely at low-energy. TRIM (The TRansport of Ions in Matter), a Monte-Carlo simulation program, was adapted to study sputtering yields, and energy and angular distributions of sputtered atoms. Simulations were run at various combinations of ion energy and ion incidence angle. TRIM did not prove to be an adequate model for low-energy sputtering. Experimental measurements of sputtering were made using both Rutherford backscattering spectrometry (RBS) and mass-loss methods. Sputtering was performed in a small vacuum facility using an ion gun. For the RBS technique, sputtered material was collected on aluminum foil substrates. The area density of the deposited Mo film on the substrates was measured using RBS. These measurements enabled calculation of differential sputtering yields, which were integrated to find the total sputtering yield. Sputtering yield was found by the mass-loss technique by simply comparing the mass of the sample both before and after sputtering using a microbalance. Sputtering yields at 100 eV, 90 eV, 80 eV, 70 eV, and 60 eV were found using the RBS technique. The mass-loss technique was only successful in the 80 eV experiment. The experimental results were unexpected. The measured sputtering yields were significantly higher than those reported by other researchers. Also, sputtering yields were found to increase with decreasing ion energy from 90 eV down to 60 eV. / Master of Science

This paper describes the construction of a positive ion source of the electrodeless discharge type and may be divided into two main topis; (1) the radio frequency oscillator and power amplifier and associated power supply and (2) the ionization chamber.

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