ogurel thz-bio v4
TRANSCRIPT
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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