TY  - JOUR
AU  - Giannos, Thomas
AU  - Lešnik, Samo
AU  - Bren, Urban
AU  - Hodošček, Milan
AU  - Domratcheva, Tatiana
AU  - Bondar, Ana-Nicoleta
TI  - CHARMM Force-Field Parameters for Morphine, Heroin, and Oliceridine, and Conformational Dynamics of Opioid Drugs
JO  - Journal of chemical information and modeling
VL  - 61
IS  - 8
SN  - 0095-2338
CY  - Washington, DC
PB  - American Chemical Society
M1  - FZJ-2021-06115
SP  - 3964 - 3977
PY  - 2021
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - 34351148
UR  - <Go to ISI:>//WOS:000688241800022
DO  - DOI:10.1021/acs.jcim.1c00667
UR  - https://juser.fz-juelich.de/record/904545
ER  -