Other Biochemistry, Biophysics, and Structural Biology Commons^™

Computer Simulations Of Enzymes, Jianzhuang Yao

Doctoral Dissertations

Enzymes are important catalysts in living systems, and understanding catalytic mechanisms of enzymes is an important task for modern biophysics and biochemistry. Computer simulations have emerged as very useful tools for understanding how enzymes work. In this dissertation, QM/MM MD simulations were applied to study the catalytic mechanisms of several enzymes, including sedolisin, S-adenosyl-L-methionine (AdoMet)-dependent methyltransferases, and salicylic acid binding protein 2. For sedolisin, we focus on the acylation and deacylation reactions catalyzed by the enzymes. We proposed a general acid/base mechanism involving the Glu/Asp residues at the active site. MD and QM/MM free energy simulations on pro-kumamolisin show that …

Comparative Genomics Of Microbial Chemoreceptor Sequence, Structure, And Function, Aaron Daniel Fleetwood

Doctoral Dissertations

Microbial chemotaxis receptors (chemoreceptors) are complex proteins that sense the external environment and signal for flagella-mediated motility, serving as the GPS of the cell. In order to sense a myriad of physicochemical signals and adapt to diverse environmental niches, sensory regions of chemoreceptors are frenetically duplicated, mutated, or lost. Conversely, the chemoreceptor signaling region is a highly conserved protein domain. Extreme conservation of this domain is necessary because it determines very specific helical secondary, tertiary, and quaternary structures of the protein while simultaneously choreographing a network of interactions with the adaptor protein CheW and the histidine kinase CheA. This dichotomous …

Applications And Improvements In The Molecular Modeling Of Protein And Ligand Interactions, Jason Bret Harris

Doctoral Dissertations

Understanding protein and ligand interactions is fundamental to treat disease and avoid toxicity in biological organisms. Molecular modeling is a helpful but imperfect tool used in computer-aided toxicology and drug discovery. In this work, molecular docking and structural informatics have been integrated with other modeling methods and physical experiments to better understand and improve predictions for protein and ligand interactions. Results presented as part of this research include:

1.) an application of single-protein docking for an intermediate state structure, specifically, modeling an intermediate state structure of alpha-1-antitrypsin and using the resulting model to virtually screen for chemical inhibitors that can …

Acceleration And Verification Of Virtual High-Throughput Multiconformer Docking, Sally Rose Ellingson

Doctoral Dissertations

The work in this dissertation explores the use of massive computational power available through modern supercomputers as a virtual laboratory to aid drug discovery. As of November 2013, Tianhe-2, the fastest supercomputer in the world, has a theoretical performance peak of 54,902 TFlop/s or nearly 55 thousand trillion calculations per second. The Titan supercomputer located at Oak Ridge National Laboratory has 560,640 computing cores that can work in parallel to solve scientific problems. In order to harness this computational power to assist in drug discovery, tools are developed to aid in the preparation and analysis of high-throughput virtual docking screens, …

Natural Phenomena As Potential Influence On Social And Political Behavior: The Earth’S Magnetic Field, Jackie R. East

Theses and Dissertations--Political Science

Researchers use natural phenomena in a number of disciplines to help explain human behavioral outcomes. Research regarding the potential effects of magnetic fields on animal and human behavior indicates that fields could influence outcomes of interest to social scientists. Tests so far have been limited in scope. This work is a preliminary evaluation of whether the earth’s magnetic field influences human behavior it examines the baseline relationship exhibited between geomagnetic readings and a host of social and political outcomes. The emphasis on breadth of topical coverage in these statistical trials, rather than on depth of development for any one model, …