Terahertz dielectric study of bio-molecules using time-domain spectrometry and molecular dynamics simulations

Abstract

Terahertz frequency domain constitutes the least explored part of electromagnetic spectrum. At the same time plenty of physical phenomena occurs on picoseconds to nanosecond time-scale and have and can be monitored/controlled/studied by THz and sub-THz waves. Since the advent of photo-conductive generation followed by invention of the first THz-TDS system, research in this field made a huge progress, although still possess a considerable potential for growth. Alongside advances in generation and detection of THz radiation simulation tools are becoming increasingly important and facilitate interpretation of the experimental results. Thesis comprises three related subjects, namely the processing of THz-TDS raw data, analysis of protein solvation dynamics by simulations and experimental investigation of water-protein solution at different concentrations. Experimental works in this thesis is performed using THz-TDS (normally covers 0.1-4 THz domain) and quasi-optical bench which covers the 75-325 GHz frequency bands. Molecular dynamics simulations were conducted in Gromacs package with a purely mechanical force field. The thesis is organized in the following way: chapter 1 introduces THz frequency domain to the reader, by describing its location in the electromagnetic spectrum, the physical phenomena that falls to THz domain, the main applications of THz radiation and overview of the mechanism of interaction between THz waves and bio-molecules. Second chapter outlines the principles of operation, physical processes and areas of application of THz-TDS. It is completed with a detailed description of the THz-TDS available in our laboratory. Third chapter gives a general picture of data processing related to material parameter extraction from time-domain response of the sample recorded by THz-TDS. Then it goes into details of associated error analysis, introducing the uncertainty caused by utilization of approximated transfer function. The application of the accurate algorithm for sample thickness determination based on its THz response is also presented in the third chapter. The fourth chapter discusses the application of Gromacs molecular dynamics simulations for the study of solvation dynamics of four selected proteins, namely TRP-tail, TRP-cage, BPTI and lysozyme proteins. All the water molecules solvating protein are divided into buried in the protein interior structure and the ‘on-surface’ water molecules. The later is shown to have similar properties for all proteins, while the former serve as the origin for the differences in solvation dynamics of proteins. Further in this chapter the radius of hydration shell and its dependence on the protein structure is investigated using vibrational density of states of solvating water molecules. The experimental investigation of the lysozyme, myoglobin and BSA proteins solutions performed over 0.22-0.325 THz domain using the PNA-driven quasi-optical bench is described in chapter 5. The relative absorption of protein molecules in solution and the hydration shell depth is also estimated. The last chapter concludes the thesis and outlines some future prospects.