The sequence-dependence of biomolecular interactions involving nucleic acids and proteins is essential for numerous processes inside the cell. Insights into the underlying molecular mechanisms have... Show moreThe sequence-dependence of biomolecular interactions involving nucleic acids and proteins is essential for numerous processes inside the cell. Insights into the underlying molecular mechanisms have been obtained using various biochemical and biophysical methods on two different levels — bulk and single-molecule. These have complemented each other as single-molecule studies excel in observing multi-state dynamic interactions, but perform only at low throughput; while bulk studies can probe many different sequences simultaneously, but providing limited kinetic information. To unite the strengths of both levels, we developed high-throughput Single-molecule Parallel Analysis for Rapid eXploration of Sequence space (SPARXS), that allows the study of molecular structure, kinetics and interactions for thousands of different sequences simultaneously at the single-molecule level. We, for the first time, combine single-molecule fluorescence with next-generation Illumina sequencing. As a proof of principle we apply SPARXS to study the sequence-dependent kinetics of the four-way DNA Holliday junction, occurring among others during homologous recombination. Using SPARXS we observe the dynamic behavior of 120,000 Holliday junction molecules covering 3750 distinct core sequences, a result unattainable with previous techniques. Overall, the mechanistic insights obtained using SPARXS will give an entirely new view on the relationship between sequence, structure and function. Show less
The increased availability of accelerator technology in modern supercomputers forces users to redesign their algorithms. These accelerators are specifically designed to offer huge amounts of... Show moreThe increased availability of accelerator technology in modern supercomputers forces users to redesign their algorithms. These accelerators are specifically designed to offer huge amounts of parallel compute power. In this thesis I show how to harness the power of these parallel processors for astrophysical simulations. I start with an introduction that presents the developments in astrophysical algorithms and used hardware since the 1960__s till today. In the following scientific chapters I discuss the use of GPU accelerator technology for direct N-body methods and for the more advanced hierarchical algorithms. These advanced algorithms are more complex to implement on large parallel architectures, but by redesigning the algorithms it is possible to take advantage of the GPU. The developed algorithms are applied to simulate galaxy mergers to explain discrepancies in observational results. In the simulations we test different merger configurations and try to match the results with observational data. The final chapter shows how to scale the developed software code to thousands of GPUs as available in the Titan supercomputer. The in this thesis developed and presented algorithms allow astronomers to take advantage of the new GPU technology and thereby run simulations that contain thousand times more particles than was possible before Show less
