Molecular level studies of water-mediated interactions and their role in biomolecular self-assembly.

摘要

This thesis focuses on the theoretical and computational studies of the role of water and water-mediated interactions in biological self-assembly. The work specifically focuses on the response of biological self-assembly phenomena to thermodynamic stresses, such as high temperature and pressure, and extremes in solution conditions (e.g., the presence of salts, additives, or denaturants). The response of biological systems to thermodynamic perturbations, apart from their direct relevance to engineering applications, also provides useful insights into the role of key intermolecular interactions that drive the assembly.; At the simplest level of description, the effects of environmental stress on biomolecular stability and phase behavior can be understood by studying their effects on primary stabilizing interactions, namely, hydrophobic interactions. Exhaustive studies are presented here on the temperature, pressure, and salt concentration dependence of two- and three-particle hydrophobic interactions between molecular solutes. Our investigations of salt effects on hydrophobic phenomena show a clear strengthening of hydrophobic interactions with addition of NaCl. Further, preferential exclusion of salt ions from the region vicinal to hydrophobic solutes can be used in a theoretical approach to predict the changes in the stability of different conformations of a hydrophobic solute.; We designed a model hydrophobic polymer that is sufficiently large to encompass the nanometer and larger scale hydrophobic phenomena through studies of its conformational equilibrium. The free energy landscape of this polymer was characterized in water at various temperatures and pressures, and in aqueous solutions of additives. The effects of environmental stress on the relative stability of folded and unfolded polymer conformations allow us to address the recently posited crossover of hydrophobic effects at large length scales. (Abstract shortened by UMI.)