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@ARTICLE{Hoang:1039818,
author = {Hoang, Gia Linh and Röck, Manuel and Tancredi, Aldo and
Magauer, Thomas and Mandelli, Davide and Schulz, Jörg B.
and Krauss, Sybille and Rossetti, Giulia and Tollinger,
Martin and Carloni, Paolo},
title = {{R}efining {L}igand {P}oses in {RNA}/{L}igand {C}omplexes
of {P}harmaceutical {R}elevance: {A} {P}erspective by
{QM}/{MM} {S}imulations and {NMR} {M}easurements},
journal = {The journal of physical chemistry letters},
volume = {16},
number = {7},
issn = {1948-7185},
address = {Washington, DC},
publisher = {ACS},
reportid = {FZJ-2025-01815},
pages = {1702 - 1708},
year = {2025},
abstract = {Predicting the binding poses of ligands targeting RNAs is
challenging. Here, we propose that using first-principles
quantum mechanics/molecular mechanics (QM/MM) simulations,
which incorporate automatically polarization effects, can
help refine the structural determinants of ligand/RNA
complexes in aqueous solution. In fact, recent advances in
massively parallel computer architectures (such as exascale
machines), combined with the power of machine learning, are
greatly expanding the domain of applicability of these types
of notoriously expensive simulations. We corroborate this
proposal by carrying out a QM/MM-based study on a ligand
targeting CAG repeat-RNA, involved in Huntington’s
disease. The calculations indeed show a clear improvement in
the ligand binding properties, and they are consistent with
the NMR measurements, also performed here. Thus, this type
of approach may be useful for practical applications in the
design of ligands targeting RNA in the near future.},
cin = {INM-11 / INM-9},
ddc = {530},
cid = {I:(DE-Juel1)INM-11-20170113 / I:(DE-Juel1)INM-9-20140121},
pnm = {5241 - Molecular Information Processing in Cellular Systems
(POF4-524) / DFG project G:(GEPRIS)491111487 -
Open-Access-Publikationskosten / 2025 - 2027 /
Forschungszentrum Jülich (OAPKFZJ) (491111487)},
pid = {G:(DE-HGF)POF4-5241 / G:(GEPRIS)491111487},
typ = {PUB:(DE-HGF)16},
doi = {10.1021/acs.jpclett.4c03456},
url = {https://juser.fz-juelich.de/record/1039818},
}