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@ARTICLE{Scherlo:1047547,
author = {Scherlo, Marvin and Phillips, Dominic and Künne, Ricarda
and Ippoliti, Emiliano and Gerwert, Klaus and Kötting,
Carsten and Carloni, Paolo and Mey, Antonia S. J. S. and
Rudack, Till},
title = {{IR} {S}pectroscopy: {F}rom {E}xperimental {S}pectra to
{H}igh-{R}esolution {S}tructural {A}nalysis by {I}ntegrating
{S}imulations and {M}achine {L}earning},
journal = {The journal of physical chemistry / B},
volume = {129},
number = {45},
issn = {1520-6106},
address = {Washington, DC},
publisher = {Americal Chemical Society},
reportid = {FZJ-2025-04373},
pages = {11652–11665},
year = {2025},
abstract = {Understanding biomolecular function at the atomic scale
requires detailed insight into the structural changes
underlying dynamic processes. Vibrational infrared (IR)
spectroscopy─when paired with biomolecular simulations and
quantum-chemical calculations─determines bond length
variations on the order of 0.01 Å, providing insights into
these structural changes. Here, we address the forward
problem in IR spectroscopy: predicting high-accuracy
vibrational spectra from known molecular structures
identified by biomolecular simulations. Solving this problem
lays the groundwork for the inverse problem: inferring
structural ensembles directly from experimental IR spectra.
We evaluate two computational approaches, normal-mode
analysis and Fourier-transformed dipole autocorrelation,
against experimental IR spectra of N-methylacetamide, a
prototypical model for peptide bond vibrations. Spectra are
derived from simulation models at multiple levels of theory,
including hybrid quantum mechanics/molecular mechanics,
machine-learned, and classical molecular mechanics
approaches. Our results highlight the capabilities and
limitations of current theoretical biophysical approaches to
decode structural information from experimental vibrational
spectroscopy data. These insights underscore the potential
of future artificial intelligence (AI)-enhanced models to
enable direct IR-based structure determination. For example,
resolving the so-far experimentally inaccessible structures
of toxic oligomers involved in neurodegenerative diseases,
enabling improved disease diagnostics and targeted
therapies.},
cin = {INM-9},
ddc = {530},
cid = {I:(DE-Juel1)INM-9-20140121},
pnm = {5241 - Molecular Information Processing in Cellular Systems
(POF4-524)},
pid = {G:(DE-HGF)POF4-5241},
typ = {PUB:(DE-HGF)16},
doi = {10.1021/acs.jpcb.5c04866},
url = {https://juser.fz-juelich.de/record/1047547},
}