In the first study, we use all-atom physics-based MD simulation with explicit water to sample the equilibrium arrangement of water surrounding a single molecule of hydrophobic solute; These include methane, the simplest hydrophobic solute, and Buckminsterfullerene, a nanoscale hydrophobic sphere. The hydrophobic effect (the property that non-polar entities tend to aggregate in water) is a major stabilizing force of protein, nucleic acid and lipid structure, and a driving force of macromolecular self-organization. However, the physical origin of the hydrophobic effect is still poorly understood. Structural properties of water due to the hydrophobic effect, and the effect of solute size, are studied in detail. The hydrophobic hydration of Buckminsterfullerene in water is of interest as it has potential in pharmaceutical and nano-material applications, and is an excellent model system, as it is a large and almost spherically symmetrical solute, allowing for spherical averaging, which is extremely sensitive, enhancing signal while canceling noise. Our second area of study focuses on the simulation of a large molecular machine, RNA polymerase II (pol II), a key player in the transcription of messenger RNA from template DNA, a basic step in the Central Dogma of Molecular Biology. In this molecular machine, a structurally conserved element, the trigger loop (TL), has been suggested to play a key role in both selection and catalysis of transcription although the mechanism is still far from understood. Recently resolved X-ray structures of the RNA pol II transcription elongation complex show extensive interactions of the TL with a correctly matched nucleotide in the active site. We use all-atom MD simulation to study the RNA pol II system; To our knowledge, this is the first such simulation. We show that the protein-DNA-RNA complex is stable for a period of 46 ns in simulation. Our analysis targets an absolutely conserved histidine residue in the TL. In addition to the wild-type (WT) complex, we also simulate single point mutations of His1085 to the amino acids phenylalanine and tyrosine, previously experimentally shown to have an effect on transcription elongation, and we investigate different protonation states for His1085, inaccessible to experimental observation. We separate the contribution of hydrogen bond interactions and salt bridge interactions to this interaction and show how both contribute to the stabilization of a closed conformation suggested to have catalytic significance. In the third study, we use a coarse-grained dynamics approach to study conformational change in proteins. Protein structures are inherently dynamic and movement is crucial to their function. Many proteins have been crystallographically solved in several conformations. In order to understand the biological function of these proteins we must understand the pathways that a protein follows between conformations. In addition, there may be long-lived intermediate states that we would like to be able to predict given the known crystal structures. Ideally, we would like to study these transitions in as much detail as possible, however, biologically relevant motions often happen on a timescale of milliseconds to seconds, and involve many tens and hundreds of thousands of atoms, making an atomically resolved simulation infeasible. This has prompted an interest in methods that study protein dynamics on a coarse-grained level. We present a new morphing method between two known crystal structures. Our novel method seeks to recreate biologically relevant pathways by interfering as little as possible in the trajectory chosen by the protein, yet still connecting the two...