Arrangement
of Fibril Side Chains Studied by Molecular
Dynamics and Simulated Infrared and Vibrational Circular Dichroism
Spectra
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Abstract
Highly ordered assemblies of β-sheet-forming
peptide and
protein fibrils have been the focus of much attention because of their
multiple and partially unknown biological functions, in particular
as related to degenerative neuronal disorders. Recently, vibrational
circular dichroism (VCD) spectra have been shown to provide a unique
means of detection for such extended structures utilizing modes of
the peptide main chain backbone. In the case of poly-glutamic acid,
surprising VCD responses were also found for side chain modes. In
this study, in an attempt to explain this latter observation and obtain
a link between fibrillar structure and its optical spectral properties,
molecular dynamics (MD) methods are used to model the geometry and
dynamics of assemblies containing repeating β-strands of Glu<sub><i>n</i></sub>. A crystal-like model was adopted for the
MD structure simulations. Infrared and VCD spectra for segments of
MD modeled fibrillar geometries were first calculated using density
functional theory (DFT), and then, those parameters were applied to
larger structures by means of Cartesian coordinate transfer (CCT)
of atomic tensors from the segments. The computations suggest the
side chains exhibit residual conformational constraints, resulting
in local coupling giving rise to non-negligible VCD intensity, albeit
with an overall broad distribution. Calculated spectral distributions
are qualitatively consistent with the experimental results but do
differ in magnitude. The possibility of realistic modeling of vibrational
spectra significantly broadens the potential for application of optical
spectroscopies in structural studies of these aggregated biopolymers