Proteins exhibit dynamic behavior with their normal modes

vibrating at terahertz frequencies. Building on previous studies,

TDS experiments were performed identifying specific absorption

of terahertz radiation by met-hemoglobin and myoglobin, thus

verifying the “Protein Electrodynamic” hypothesis. Subsequent

studies have also demonstrated the utility of terahertz radiation as

a potential diagnostic modality for “Terahertz Medicine.”

I. INTRODUCTION AND BACKGROUND

roteins, often depicted as static structures, are quite

dynamic, with such motions being investigated

theoretically [1,2] and experimentally [3–6]. These vibrations

are essential to protein function [7, 8] and currently three

protein motion databases exist, cataloguing their normal

modes, experimental data, and molecular dynamics trajectories.

[9-11]

Using these databases, one study of over 4,000 example

proteins showed the majority had less than two low-frequency

modes [12], with these vibrations relating to conformational

shifts [13], and the lowest-frequency NMAs predicting, too, the

direction of these conformational changes. [14] Molecular

dynamics calculations and experimental studies have shown

these large-scale ‘low-frequency’ normal modes vibrate

generally in the 1012

hertz (terahertz) range. Neutron scattering

experiments on myoglobin, for example, showed a major

spectral peak between 450 – 600 GHz (15 – 20 cm-1

) [15]

While proteins are typically isoelectric, they exhibit surface

charges and dipoles [16, 17] Accelerating (vibrating) charges

radiate and absorb electromagnetic energy, as should proteins

as well: a concept we call: “Protein Electrodynamics.”

To verify this, time domain terahertz spectroscopy (TDS)

was performed on human met-hemoglobin at the Pohang

Accelerate Laboratory. [18, 19] Three major spectroscopic

patterns were observed: (1) broad absorption above 1.5THz, (2)

two mid-range resonances at 0.8 and 1.3THz, and (3)

lower-frequency emission. These spectroscopic features

correspond to the known characteristics of protein vibrations: a

broad spectrum of higher frequencies extending into the

infrared, as well as the functionally significant lower frequency

modes. [20] Beyond establishing proof-of-concept, such

experiments (and others [21]) have prepared the groundwork to

apply the ‘protein electrodynamic’ concept to novel approaches

in medical diagnosis and therapeutics, which we term,

“Terahertz Medicine.”

II. RESULTS

Following up on these studies, further experiments were

performed using the same procedures as outlined in [20] with

both bovine and human met-hemoglobin as well as human

myoglobin. In addition to reproducing the spectroscopic

features previously described, including the high-frequency

Stokes shift, other important results were obtained:

First, there was a difference at the higher (~ 1.1 – 1.5 THz)

frequencies between myoglobin and hemoglobin, of which the

former, a smaller molecule, absorbed more significantly at

these higher frequencies. Second, there was a species specific

difference between human and bovine hemoglobin at

approximately 0.6 THz, with human hemoglobin absorbing at

this frequency and the bovine variety showing the opposite. As

the three proteins share the same ‘globin’ fold, there were, also,

as expected, similarities between the three proteins, for

example with their lack of absorption at 0.5 THz.

This research further confirms the ‘Protein Electrodynamic’

hypothesis: that proteins interact with terahertz radiation, as

related to the underlying protein dynamics. The idea that

individual proteins might express unique spectroscopic

signals—coupled with the imaging properties of terahertz

radiation more generally—suggests an anatomic-molecular

imaging modality of great sensitivity and specificity, without

requiring exogenous probes, labels, or contrast.

III. DISCUSSION & CONCLUSIONS

Following up on these studies, further TDS experiments

were also conducted with both cancer and Alzheimer’s tissues

[22 – 28]. While these studies were not intended to elicit

specific protein spectral features, they substantiate spectral

normal and pathologic specimens can be distinguished

spectroscopically, thus serving as a basis for novel, more

biologically specific, medical diagnostic modalities. We

envision, too, that terahertz radiation, resonantly modulating

protein motions and hence protein function, can serve as a basis

entirely novel and powerful methods of medical therapeutics.

The use of tunable (CW) THz sources, particularly in the

sub-THz range, will be particularly important for such clinical

applications in order to minimize water absorption and

maximize radiative power at frequencies specific to the

proteins of interest.

Ogan Gurela,b

, Richard McKaya,c

, Seong-hoon Jeongd, Jaehun Park

d, Seong-Eon Ryu

e, Niru Nahar

f, Kubilay Sertel

f

a NovumWaves, Seoul, Korea,

b DRB Holdings, Busan, Korea,

c Full Spectrum Scientific, Princeton, USA,

d Pohang Accelerator Laboratory and

POSTECH, Pohang, Korea, e

Hanyang University, Seoul, Korea, f The Ohio State University, Columbus, Ohio, USA

Protein Electrodynamics & Terahertz Medicine: An Update

P

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