215
8 Two-Dimensional Mid-Infrared Correlation Spectroscopy in Protein Research
over a narrow range of perturbations. the main advantage of 2dCoS is that 2dCoS
probes the specific sequence of spectral intensity changes that take place during
the perturbation-controlled measurement. Whenever 2dCoS is applied to protein
studies the sequence of the secondary structure changes on the perturbation axes
is predicted from the synchronous and asynchronous changes according to Noda’s
rules [1, 6]. the sequence of events related to infrared spectra makes it possible to
elucidate the nature of the structural transitions and makes an important contribution
to finding the non-native local minima in which partially folded proteins can become
trapped. the fact that infrared 2dCoS allows the evolution of protein structures to be
explored has helped to maintain and has even intensified the interest of researchers
in the use of infrared spectroscopy to solve an old problem in protein chemistry.
Recently, interest in vibrational spectroscopy has additionally been motivated by
the fact that this technique belongs to limited group of methods employed in studies
of amyloid fibril formation. Although the studies are strongly supported by molecular dynamics (md) simulations, reliable results cannot yet be obtained because this
method is still limited to a set of small, simple protein folds [7]. For proteins with
more than approximately 100 residues, experiments generally reveal that one (or
more) intermediate is significantly populated during the folding process [8]. the
problem is that “We do not have a quantitative microscopic understanding of the
folding routes or transition states” [9]. Without knowledge of the structure of the
intermediates, the mechanisms through which the fibrillation processes proceeds
cannot be determined. moreover, the structural information for these forms is not
always available or of high resolution from X-ray crystallography or nuclear magnetic resonance (NmR) spectroscopy. these techniques are especially ill-suited for
studying noncrystalline and insoluble full-length fibrils [10]. optical spectroscopies
supported by two-dimensional correlation spectroscopy are potential alternatives
to X-ray and NmR methods in these studies [11]. In particular, infrared spectroscopy is very well suited to following the processes of fibril formation from β-type
proteins [12]. Bands between 1,611–1,630 cm
−1
are regarded as hallmarks of the
β-conformation of amyloid fibrils. In 2005, Meier in the article titled “Vibrational
spectroscopy: a ‘vanishing’ discipline?” answered “no” and argued that 2dCoS and
infrared imaging have brought many new opportunities, so vibrational spectroscopy
is far from ‘dead’ [13]. Currently, vibrational spectroscopy combined with 2dCoS
represents a particularly powerful tool in the investigation of amyloid fibril formation, which is implicated in misfolding diseases such as type II diabetes, Alzheimer’s, and Parkinson’s, which makes vibrational spectroscopy more alive than ever.
8.3 Generalized 2DCoS
Since 1993, the generalized version of 2dCoS has found numerous applications in
a variety of fields, as described by Noda and ozaki in the “handbook of vibrational
Spectroscopy” [14, 15], in the Frontiers of molecular Spectroscopy [16] and in the
text book “two-dimensional Correlation Spectroscopy—Applications in vibrational
8 Two-Dimensional Mid-Infrared Correlation Spectroscopy in Protein Research
over a narrow range of perturbations. the main advantage of 2dCoS is that 2dCoS
probes the specific sequence of spectral intensity changes that take place during
the perturbation-controlled measurement. Whenever 2dCoS is applied to protein
studies the sequence of the secondary structure changes on the perturbation axes
is predicted from the synchronous and asynchronous changes according to Noda’s
rules [1, 6]. the sequence of events related to infrared spectra makes it possible to
elucidate the nature of the structural transitions and makes an important contribution
to finding the non-native local minima in which partially folded proteins can become
trapped. the fact that infrared 2dCoS allows the evolution of protein structures to be
explored has helped to maintain and has even intensified the interest of researchers
in the use of infrared spectroscopy to solve an old problem in protein chemistry.
Recently, interest in vibrational spectroscopy has additionally been motivated by
the fact that this technique belongs to limited group of methods employed in studies
of amyloid fibril formation. Although the studies are strongly supported by molecular dynamics (md) simulations, reliable results cannot yet be obtained because this
method is still limited to a set of small, simple protein folds [7]. For proteins with
more than approximately 100 residues, experiments generally reveal that one (or
more) intermediate is significantly populated during the folding process [8]. the
problem is that “We do not have a quantitative microscopic understanding of the
folding routes or transition states” [9]. Without knowledge of the structure of the
intermediates, the mechanisms through which the fibrillation processes proceeds
cannot be determined. moreover, the structural information for these forms is not
always available or of high resolution from X-ray crystallography or nuclear magnetic resonance (NmR) spectroscopy. these techniques are especially ill-suited for
studying noncrystalline and insoluble full-length fibrils [10]. optical spectroscopies
supported by two-dimensional correlation spectroscopy are potential alternatives
to X-ray and NmR methods in these studies [11]. In particular, infrared spectroscopy is very well suited to following the processes of fibril formation from β-type
proteins [12]. Bands between 1,611–1,630 cm
−1
are regarded as hallmarks of the
β-conformation of amyloid fibrils. In 2005, Meier in the article titled “Vibrational
spectroscopy: a ‘vanishing’ discipline?” answered “no” and argued that 2dCoS and
infrared imaging have brought many new opportunities, so vibrational spectroscopy
is far from ‘dead’ [13]. Currently, vibrational spectroscopy combined with 2dCoS
represents a particularly powerful tool in the investigation of amyloid fibril formation, which is implicated in misfolding diseases such as type II diabetes, Alzheimer’s, and Parkinson’s, which makes vibrational spectroscopy more alive than ever.
8.3 Generalized 2DCoS
Since 1993, the generalized version of 2dCoS has found numerous applications in
a variety of fields, as described by Noda and ozaki in the “handbook of vibrational
Spectroscopy” [14, 15], in the Frontiers of molecular Spectroscopy [16] and in the
text book “two-dimensional Correlation Spectroscopy—Applications in vibrational