Dynamical Properties of Biomolecules, Ions and Glass-Forming Liquids

Abstract

The conformational dynamics plays a significant role in a wide range of biological systems, from small RNA molecules to the large-scale ribonucleoprotein assemblies, in which ions are found critical and have notable structural and functional impacts. In the glass-forming liquids, the structural dynamics also calls for further investigations and deeper understandings. To this end, using four distinct chapters, this dissertation discusses the ion-related conformational dynamics in various scales of biomolecular systems, as well as the fluctuation effects in the glass-forming liquids. In chapter 1, we investigate the dynamics of ions and water molecules in the outer solvation sphere of a widely studied 58-nucleotide rRNA fragment. Molecular dynamics (MD) simulations with explicit solvent molecules and atomic details are performed for the RNA fragment in ionic solution. We determine all of the association sites and spatial distributions of residence times for Mg2+, K+, and water molecules in those sites. In accordance to the analysis of the dynamics of the RNA fragment, we provide insights into how the dynamics of ions and water molecules are intricately linked with the kinetics of the RNA fragment. In addition, the long-lived sites for Mg2+ ions identified from the simulation agree with the metal ion locations determined in the X-ray structure. The excess ion atmosphere around the RNA fragment is calculated and compared with the experimental measures. The results from this study indicate that the 58-mer rRNA fragment in ionic solution forms a complex polymer that is encased by a fluctuating network of ions and water. In chapter 2, the conformational dynamics of a large-scale ribonucleoprotein assembly, ribosome, is studied with molecular dynamics simulations with a newly developed model that accounts for electrostatic and ionic effects on the biomolecules. In this study, an all-atom structure based model is constructed with explicit representations of non-hydrogen atoms from biomolecules and diffuse ions. Implicit treatment is applied to the solvent molecules with the solvation effect associated with diffuse ions described by effective potentials. Parameters in this model are refined against explicit solvent simulations and experimental measures. This model with refined parameters is able to capture the excess Mg2+ ions for prototypical RNA systems and their dependence on the Mg2+ concentrations. Motivated by this, we apply the model to a bacterial ribosome and find that the position of the extended L1 stalk region can be controlled by the diffuse ions. This simulation also indicated ion-induced long-range interactions between L1 stalk and tRNA, which provides insights into the impact of ions on the functional rearrangements of ribosome. In chapter 3, we focus on the dynamics of the glass-forming liquids. In this study, we generalized the Adam-Gibbs model of relaxation in glass-forming liquids and take into account the fluctuations in the number of molecules inside the cooperative rearranging region. We obtain the expressions of configurational fractions at the glass-transition temperature with and without the fluctuation effect in Adam-Gibbs model, and determine the configurational fraction for several glass-forming liquids at glass-transition temperature in the absence of fluctuation effects. A connection between the β Kohlrausch-Williams-Watts parameters and the configurational fraction at the glass-transition temperature is also reported in this study. In chapter 4, we apply the model developed in chapter 2 to a ribosome structure to investigate the effects of diffuse ions on the aminoacyl-tRNA (aa-tRNA) accommodation process. The aa-tRNA accommodation is a critical step in the tRNA selection process which serves the purpose of protein synthesis in the ribosome. Experimental and computational efforts were made to reveal the mechanism and the energetic properties of the accommodation process, while the effects from diffuse ions on this process remain elusive. To this end, we design and perform MD simulations of ribosome structure with different treatment of electrostatics and diffuse ions in the system. Simulations with various ionic concentrations are also performed to study the concentration effects. The simulation trajectories indicate that diffuse ions can facilitate the aa-tRNA accommodation process and stabilize the accommodated configurations. In addition, we observe that Mg2+ ions play critical roles in stabilizing the accommodated configurations and a few millimolar change of Mg2+ concentration can alter the tendency of the tRNA configurational change during the accommodation process. This result shed light on the investigations of suitable ionic environment for the tRNA selection in the ribosome. It will be fruitful to extend this strategy into the investigations of other conformational rearrangements in the ribosome, such as tRNA translocation and subunit rotation, which will provide us with deeper understanding about the functional mechanism of the ribosome.