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@ARTICLE{Giannos:904545,
author = {Giannos, Thomas and Lešnik, Samo and Bren, Urban and
Hodošček, Milan and Domratcheva, Tatiana and Bondar,
Ana-Nicoleta},
title = {{CHARMM} {F}orce-{F}ield {P}arameters for {M}orphine,
{H}eroin, and {O}liceridine, and {C}onformational {D}ynamics
of {O}pioid {D}rugs},
journal = {Journal of chemical information and modeling},
volume = {61},
number = {8},
issn = {0095-2338},
address = {Washington, DC},
publisher = {American Chemical Society},
reportid = {FZJ-2021-06115},
pages = {3964 - 3977},
year = {2021},
abstract = {Opioid drug binding to specialized G protein-coupled
receptors (GPCRs) can lead to analgesia upon activation via
downstream Gi protein signaling and to severe side effects
via activation of the β-arrestin signaling pathway.
Knowledge of how different opioid drugs interact with
receptors is essential, as it can inform and guide the
design of safer therapeutics. We performed quantum and
classical mechanical computations to explore the potential
energy landscape of four opioid drugs: morphine and its
derivatives heroin and fentanyl and for the unrelated
oliceridine. From potential energy profiles for bond twists
and from interactions between opioids and water, we derived
a set of force-field parameters that allow a good
description of structural properties and intermolecular
interactions of the opioids. Potential of mean force
profiles computed from molecular dynamics simulations
indicate that fentanyl and oliceridine have complex energy
landscapes with relatively small energy penalties,
suggesting that interactions with the receptor could select
different binding poses of the drugs.},
cin = {IAS-5 / INM-9},
ddc = {540},
cid = {I:(DE-Juel1)IAS-5-20120330 / 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},
pubmed = {34351148},
UT = {WOS:000688241800022},
doi = {10.1021/acs.jcim.1c00667},
url = {https://juser.fz-juelich.de/record/904545},
}