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. Cross-correlations between water and side-chains are anti-correlated, making the solvation faster.

In Part III, we study the solvation dynamics of DNA. In Chapter 8 we briefly review the literature in this field. In Chapter 9 we employ multiple theoretical and simulation analyses to understand the origin of the long time power law behaviour in the solvation dynamics of DNA. We find that electrolytic friction and movement of ions along the DNA backbone could be responsible for this mysterious behaviour.

Part IV deals with the different phases of water and their transitions. In Chapter 10, we discuss the phase diagram of water and its multiple regions. In Chapter 11 we compare the solid-liquid interfaces in TIP4P/ice and mW water models with Lennard-Jones argon. We find that ice-water interface is much sharper than its LJ counterpart, mainly due to sharp change in rotational entropy. We also study the growth rate of ice at different temperatures and compare it with experimental observations. We find that Wilson-Frenkel equation of crystal growth breaks down at higher temperatures. In Chapter 12, we observe the pressure induced crystal to glass transition in low density ice. High density crystalline ice show no transition. We find that hydrogen bond defects can be used as effective order parameters to study these phase transitions. At very high pressure (150 kbar), we observe the emergence of crystalline order from the disordered glassy phase.

In Part V, we study of a small medicinally important molecule metformin. In Chapter 13, we develop a force field of this molecule and validate it with multiple experimental observations. We study the structural and dynamical features of metformin and develop a free energy landscape of DNA-metformin interactions.

The last part of the thesis (Part VI) contains a single chapter (Chapter 14) which includes the concluding remarks and the future plans and research prospects derived from this thesis.