The hydrophobic effect plays an important role in formation of biomolecular aggregates and their interactions. For example, it is thought to be the main driving force in guiding protein folding [13]: a large number of proteins possess hydrophobic cores. Similarly, the coiled-coil structures often form around a central hydrophobic axis, and the energetics of protein tertiary structure are mostly caused by the hydrophobic effect.
A minimal set of model systems to study hydrophobicity consists of two small solutes in water. Because of the influence of hydrophobic effect, the most stable configuration of two apolar molecules in aqueous solution should be when they are in contact (contact potential minimum configuration). Another stable configuration is the so-called solvent-separated configuration, in which a layer of water molecules is sandwiched between two solutes (see the right hand side of Fig. 1). Between these two stable configurations, there is an energy barrier in the potential of mean force (PMF). The height of the energy barrier is critical in the chemical reaction between two solutes in aqueous solutions. Given its importance in understanding the interaction between apolar solutes in water, a large portion of the present study is devoted to investigate the shape and depth of the PMF between two small hydrophobic solutes, in the hope of probing the multifaceted effect under various conditions.
Methane is the most basic and smallest molecule in the paraffin series. For simplicity, it is chosen as the apolar solute in this and many other similar studies [5,10,24,32,19]. Because of the low solubility of methane in water, direct experimental measurement is not feasible. Instead, computer simulations have been an invaluable tool in the understanding of this model system. The hydrophobicity is influenced by many factors, including temperature, density, water models, and force field parametrization, which have been investigated by various groups [18,23,22,20]. This study differs from earlier works in that we compared the PMF calculated from classical force-field molecular dynamics simulation (MD) and quantum mechanical MD, and then we did a series of simulations to examine the dependence of the PMF on the short-range intermolecular repulsive interactions.
This thesis is organized as follows. Chapter 2 introduces basic water properties, including hydrogen bond network, which plays an important role in the structure of water. We also review a few commonly used water models in MD simulations. Chapter 3 discusses selective intermolecular interactions in the system. In particular, the prevalent model of intermolecular interactions used in MD, the Lennard-Jones potential, is composed of long-distance van der Waals attractive interactions and a short-distance hard-core like repulsive force. Both parts are critical in determining the shape of the PMF. Chapter 4 outlines MD simulation methods used in the current study. The connection between radial distribution functions and the PMF is explained, along with two methods for calculating the PMF. The main results are shown in Chapter 5. The PMF calculated with different forms of repulsive force is juxtaposed with results from quantum mechanical calculations. It is followed by a short discussion and conclusion.
