Observing the temperature dependent transition of the GP2 peptide using terahertz spectroscopy

The GP2 peptide is derived from the Human Epidermal growth factor Receptor 2 (HER2/nue), a marker protein for breast cancer present in saliva. In this paper we study the temperature dependent behavior of hydrated GP2 at terahertz frequencies and find that the peptide undergoes a dynamic transition between 200 and 220 K. By fitting suitable molecular models to the frequency response we determine the molecular processes involved above and below the transition temperature (TD). In particular, we show that below TD the dynamic transition is dominated by a simple harmonic vibration with a slow and temperature dependent relaxation time constant and that above TD, the dynamic behavior is governed by two oscillators, one of which has a fast and temperature independent relaxation time constant and the other of which is a heavily damped oscillator with a slow and temperature dependent time constant. Furthermore a red shifting of the characteristic frequency of the damped oscillator was observed, confirming the presence of a non-harmonic vibration potential. Our measurements and modeling of GP2 highlight the unique capabilities of THz spectroscopy for protein characterization.Yiwen Sun, Zexuan Zhu, Siping Chen, Jega Balakrishnan, Derek Abbott, Anil T. Ahuja and Emma Pickwell-MacPherso

Why is THz Sensitive to Protein Functional States? Oxidation State of Cytochrome C

Abstract: We investigate the presence of structural collective motions on a picosecond time scale for the heme protein, cytochrome c, as a function of oxidation and hydration, using terahertz (THz) time-domain spectroscopy and molecular dynamics simulations. Structural collective mode frequencies have been calculated to lie in this frequency range, and the density of states can be considered a measure of flexibility. A dramatic increase in the THz response occurs with oxidation, with the largest increase for lowest hydrations and highest frequencies. For both oxidation states the measured THz response rapidly increases with hydration saturating above ~25% (g H 2 O/g protein), in contrast to the rapid turn-on in dynamics observed at this hydration level for other proteins. Quasi-harmonic collective vibrational modes and dipole-dipole correlation functions are calculated from the molecular dynamics trajectories. The collective mode density of states alone reproduces the measured hydration dependence providing strong evidence of the existence of these collective motions. The large oxidation dependence is reproduced only by the dipole-dipole correlation function, indicating the contrast arises from diffusive motions consistent with structural changes occurring in the vicinity of a buried internal water molecule

Modeling terahertz heating effects on water

We apply Kirchhoff's heat equation to model the influence of a CW terahertz beam on a sample of water, which is assumed to be static. We develop a generalized model, which easily can be applied to other liquids and solids by changing the material constants. If the terahertz light source is focused down to a spot with a diameter of 0.5 mm, we find that the steady-state temperature increase per milliwatt of transmitted power is 1.8?C/mW. A quantum cascade laser can produce a CW beam in the order of several milliwatts and this motivates the need to estimate the effect of beam power on the sample temperature. For THz time domain systems, we indicate how to use our model as a worst-case approximation based on the beam average power. It turns out that THz pulses created from photoconductive antennas give a negligible increase in temperature. As biotissue contains a high water content, this leads to a discussion of worst-case predictions for THz heating of the human body in order to motivate future detailed study. An open source Matlab implementation of our model is freely available for use at www.eleceng.adelaide.edu.au/thz.Torben T. L. Kristensen, Withawat Withayachumnankul, Peter U. Jepsen and Derek Abbot

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

PhDTerahertz 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.Queen Mary University of London College Doctoral Training fund (now – Principal’s studentship