Structure Thermodynamics and Dynamics in Complex Systems From Stability of Biomolecules to Phase Transitions in Polymorphic Ice

Abstract

This thesis deals with the understanding of the structure, dynamics and thermodynamics in complex systems (proteins, hydration layers, DNA, ice polymorphs) by employing computer simulations, theoretical analysis, and in some cases, collaborative experimental efforts. There are mainly 5 parts with 13 chapters. In Part I, we study the effects of solvent on the structure and stabilization of insulin hexamer. In Chapter 1 we discuss the structural features of the different oligomers of insulin. Chapter 2 deals with insulin hexamer in neat water. We find that a group of ~10 water molecules present in the cavity of insulin hexamer is crucial in stabilizing the structure of the biomolecular assembly. In Chapter 3, we study the effect of ethanol on the structure of insulin hexamer. Ethanol, by virtue of its amphiphilic nature, interacts with both hydrophilic and hydrophobic residues, thereby destroying the native state structure of insulin hexamer. In Part II, we study the interactions between several proteins and water. We start with a brief introduction of the different techniques used to study protein hydration layer (PHL) in Chapter 4. In Chapter 5, we find that the protein self-interaction energy fluctuations are strongly anti-correlated to the protein-water cross interaction energy fluctuations. The total energy spectrum of protein shows bimodal 1/f noise characteristics. We posit that water exerts control over protein dynamics via an exchange of energy between these two domains. In Chapter 6, from distributions of dynamical timescales, we find that PHL contains both fast and slow water molecules. Shell-wise decomposition of the PHL demonstrates a gradual increase of dielectric constant and decrease of specific heat from the protein surface to the bulk. In chapter 7 we study the heterogeneous solvation dynamics of protein. We find that the slow component in the solvation relaxation originates from side chain and hydration layer fluctuations. Charged neighbourhood of the probe results in slower dynamics...