Hao Yin

Date of Award


Level of Access

Campus-Only Dissertation

Degree Name

Doctor of Philosophy (PhD)




Jayendran C. Rasaiah

Second Committee Member

Carl P. Tripp

Third Committee Member

Howard H. Paterson


Water in confined systems behaves differently from bulk water. It plays a role in determining protein activity and it is important to understand the structure and thermodynamic stability of these water molecules which are often hidden within cavities. In this thesis I have carried out computer simulations to determine the structure and stability of (1) water in fullerenes and smooth spherical hydrophobic cavities which mimic protein cavities (2) water in the small hydrophobic cavity of the protein interleukin-ID at room temperature and (3) water in the largest hydrophobic cavity of the thermostable protein tetrabrachion at temperatures up to 385K (92 °C). The crystal structures of interleukin l-(3 and tetrbrachion have been determined by X'ray analysis. The presence of water in the interleukin cavity is the subject of debate but there is no controversy about its presence in the large cavity of tetrabrachion. The simulations were carried out using the TIP3P model for water and the Amber force field for proteins. It is found that small nonpolar cavities can be filled at equilibrium with highly structured water clusters. The structures of the encapsulated clusters are similar to those observed experimentally in the gas phase. Water filling is highly sensitive to the size of the cavity and the strength of the interactions with the cavity wall. The investigation of water in the central hydrophobic cavity of interleukin-lD shows that it is not thermodynamically stable. In contrast to this, the hydrogen-bonded clusters of seven to nine water molecules present in the largest cavity of tetrabrachion are thermodynamically stable even at 92°C. The drying temperature of this cavity is predicted from the energy and entropy of transfer.