A putative binding model of nitazene derivatives at the μ-opioid receptor

Clayton, Joseph; Shi, Lei; Robertson, Michael J.; Skiniotis, Georgios; Michaelides, Michael; Stavitskaya, Lidiya; Shen, Jana

doi:10.1016/j.neuropharm.2025.110437

Title: A putative binding model of nitazene derivatives at the μ-opioid receptor

Journal Article · 31 July 2025 · Neuropharmacology

DOI: https://doi.org/10.1016/j.neuropharm.2025.110437 · OSTI ID:2550708

;

; Robertson, Michael J.; Skiniotis, Georgios; Michaelides, Michael;

;

Not Available

View Journal Article

Cite

Export

Save

Sponsoring Organization:: USDOE

OSTI ID:: 2550708

Journal Information:: Neuropharmacology, Journal Name: Neuropharmacology Journal Issue: C Vol. 273; ISSN 0028-3908

Publisher:: ElsevierCopyright Statement

Country of Publication:: United Kingdom

Language:: English

References (47)

Naloxone Use in Novel Potent Opioid and Fentanyl Overdoses in Emergency Department Patients Amaducci, Alexandra; Aldy, Kim; Campleman, Sharan L. JAMA Network Open, Vol. 6, Issue 8 https://doi.org/10.1001/jamanetworkopen.2023.31264	journal	August 2023
Langevin dynamics of peptides: The frictional dependence of isomerization rates ofN-acetylalanyl-N?-methylamide Loncharich, Richard J.; Brooks, Bernard R.; Pastor, Richard W. Biopolymers, Vol. 32, Issue 5 https://doi.org/10.1002/bip.360320508	journal	May 1992
π‐Hole Interactions Involving Nitro Aromatic Ligands in Protein Structures Bauzá, Antonio; Frontera, Antonio; Mooibroek, Tiddo Jonathan Chemistry – A European Journal, Vol. 25, Issue 58 https://doi.org/10.1002/chem.201903404	journal	September 2019
CHARMM-GUI: A web-based graphical user interface for CHARMM Jo, Sunhwan; Kim, Taehoon; Iyer, Vidyashankara G. Journal of Computational Chemistry, Vol. 29, Issue 11 https://doi.org/10.1002/jcc.20945	journal	March 2008
AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility Morris, Garrett M.; Huey, Ruth; Lindstrom, William Journal of Computational Chemistry, Vol. 30, Issue 16 https://doi.org/10.1002/jcc.21256	journal	December 2009
MDAnalysis: A toolkit for the analysis of molecular dynamics simulations Michaud-Agrawal, Naveen; Denning, Elizabeth J.; Woolf, Thomas B. Journal of Computational Chemistry, Vol. 32, Issue 10 https://doi.org/10.1002/jcc.21787	journal	April 2011
Settle: An analytical version of the SHAKE and RATTLE algorithm for rigid water models Miyamoto, Shuichi; Kollman, Peter A. Journal of Computational Chemistry, Vol. 13, Issue 8 https://doi.org/10.1002/jcc.540130805	journal	October 1992
Molecular dynamics of fentanyl bound to μ-opioid receptor Lipiński, Piotr F. J.; Jarończyk, Małgorzata; Dobrowolski, Jan Cz. Journal of Molecular Modeling, Vol. 25, Issue 5 https://doi.org/10.1007/s00894-019-3999-2	journal	May 2019
Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments Madhavi Sastry, G.; Adzhigirey, Matvey; Day, Tyler Journal of Computer-Aided Molecular Design, Vol. 27, Issue 3 https://doi.org/10.1007/s10822-013-9644-8	journal	March 2013
Numerical integration of the cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes Ryckaert, Jean-Paul; Ciccotti, Giovanni; Berendsen, Herman J. C. Journal of Computational Physics, Vol. 23, Issue 3 https://doi.org/10.1016/0021-9991(77)90098-5	journal	March 1977
[19] Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors Ballesteros, Juan A.; Weinstein, Harel Receptor Molecular Biology, Vol. 25, p. 366-428 https://doi.org/10.1016/S1043-9471(05)80049-7	book	January 1995
MDTraj: A Modern Open Library for the Analysis of Molecular Dynamics Trajectories McGibbon, Robert T.; Beauchamp, Kyle A.; Harrigan, Matthew P. Biophysical Journal, Vol. 109, Issue 8 https://doi.org/10.1016/j.bpj.2015.08.015	journal	October 2015
Molecular recognition of morphine and fentanyl by the human μ-opioid receptor Zhuang, Youwen; Wang, Yue; He, Bingqing Cell, Vol. 185, Issue 23 https://doi.org/10.1016/j.cell.2022.09.041	journal	November 2022
PLUMED 2: New feathers for an old bird Tribello, Gareth A.; Bonomi, Massimiliano; Branduardi, Davide Computer Physics Communications, Vol. 185, Issue 2 https://doi.org/10.1016/j.cpc.2013.09.018	journal	February 2014
Molecular dynamics simulations of water and biomolecules with a Monte Carlo constant pressure algorithm Åqvist, Johan; Wennerström, Petra; Nervall, Martin Chemical Physics Letters, Vol. 384, Issue 4-6 https://doi.org/10.1016/j.cplett.2003.12.039	journal	January 2004
Fentanyl: Receptor pharmacology, abuse potential, and implications for treatment Comer, Sandra D.; Cahill, Catherine M. Neuroscience & Biobehavioral Reviews, Vol. 106 https://doi.org/10.1016/j.neubiorev.2018.12.005	journal	November 2019
Pharmacological characterization of novel synthetic opioids: Isotonitazene, metonitazene, and piperidylthiambutene as potent μ-opioid receptor agonists De Luca, Maria Antonietta; Tocco, Graziella; Mostallino, Rafaela Neuropharmacology, Vol. 221 https://doi.org/10.1016/j.neuropharm.2022.109263	journal	December 2022
AutoDock Vina 1.2.0: New Docking Methods, Expanded Force Field, and Python Bindings Eberhardt, Jerome; Santos-Martins, Diogo; Tillack, Andreas F. Journal of Chemical Information and Modeling, Vol. 61, Issue 8 https://doi.org/10.1021/acs.jcim.1c00203	journal	July 2021
Open Binding Pose Metadynamics: An Effective Approach for the Ranking of Protein–Ligand Binding Poses Lukauskis, Dominykas; Samways, Marley L.; Aureli, Simone Journal of Chemical Information and Modeling, Vol. 62, Issue 23 https://doi.org/10.1021/acs.jcim.2c01142	journal	November 2022
Structure–Kinetics Relationships of Opioids from Metadynamics and Machine Learning Analysis Mahinthichaichan, Paween; Liu, Ruibin; Vo, Quynh N. Journal of Chemical Information and Modeling, Vol. 63, Issue 7 https://doi.org/10.1021/acs.jcim.3c00069	journal	March 2023
Prediction of Protein–Ligand Binding Poses via a Combination of Induced Fit Docking and Metadynamics Simulations Clark, Anthony J.; Tiwary, Pratyush; Borrelli, Ken Journal of Chemical Theory and Computation, Vol. 12, Issue 6 https://doi.org/10.1021/acs.jctc.6b00201	journal	May 2016
DARK Classics in Chemical Neuroscience: Etonitazene and Related Benzimidazoles Ujváry, István; Christie, Rachel; Evans-Brown, Michael ACS Chemical Neuroscience, Vol. 12, Issue 7 https://doi.org/10.1021/acschemneuro.1c00037	journal	March 2021
Synthesis, Chemical Characterization, and μ-Opioid Receptor Activity Assessment of the Emerging Group of “Nitazene” 2-Benzylbenzimidazole Synthetic Opioids Vandeputte, Marthe M.; Van Uytfanghe, Katleen; Layle, Nathan K. ACS Chemical Neuroscience, Vol. 12, Issue 7 https://doi.org/10.1021/acschemneuro.1c00064	journal	March 2021
In Vitro Functional Profiling of Fentanyl and Nitazene Analogs at the μ-Opioid Receptor Reveals High Efficacy for Gi Protein Signaling Tsai, Meng-Hua M.; Chen, Li; Baumann, Michael H. ACS Chemical Neuroscience, Vol. 15, Issue 4 https://doi.org/10.1021/acschemneuro.3c00750	journal	February 2024
DARK Classics in Chemical Neuroscience: Fentanyl Burns, S. Mallory; Cunningham, Christopher W.; Mercer, Susan L. ACS Chemical Neuroscience, Vol. 9, Issue 10 https://doi.org/10.1021/acschemneuro.8b00174	journal	January 2018
Automation of the CHARMM General Force Field (CGenFF) I: Bond Perception and Atom Typing Vanommeslaeghe, K.; MacKerell, A. D. Journal of Chemical Information and Modeling, Vol. 52, Issue 12 https://doi.org/10.1021/ci300363c	journal	November 2012
Automation of the CHARMM General Force Field (CGenFF) II: Assignment of Bonded Parameters and Partial Atomic Charges Vanommeslaeghe, K.; Raman, E. Prabhu; MacKerell, A. D. Journal of Chemical Information and Modeling, Vol. 52, Issue 12 https://doi.org/10.1021/ci3003649	journal	November 2012
PTRAJ and CPPTRAJ: Software for Processing and Analysis of Molecular Dynamics Trajectory Data Roe, Daniel R.; Cheatham, Thomas E. Journal of Chemical Theory and Computation, Vol. 9, Issue 7 https://doi.org/10.1021/ct400341p	journal	June 2013
Long-Time-Step Molecular Dynamics through Hydrogen Mass Repartitioning Hopkins, Chad W.; Le Grand, Scott; Walker, Ross C. Journal of Chemical Theory and Computation, Vol. 11, Issue 4 https://doi.org/10.1021/ct5010406	journal	March 2015
CHARMM Force Field Parameters for Nitroalkanes and Nitroarenes Klauda, Jeffery B.; Brooks, Bernard R. Journal of Chemical Theory and Computation, Vol. 4, Issue 1 https://doi.org/10.1021/ct700191v	journal	December 2007
Kinetics and Mechanism of Fentanyl Dissociation from the μ-Opioid Receptor Mahinthichaichan, Paween; Vo, Quynh N.; Ellis, Christopher R. JACS Au, Vol. 1, Issue 12 https://doi.org/10.1021/jacsau.1c00341	journal	November 2021
Glide: A New Approach for Rapid, Accurate Docking and Scoring. 1. Method and Assessment of Docking Accuracy Friesner, Richard A.; Banks, Jay L.; Murphy, Robert B. Journal of Medicinal Chemistry, Vol. 47, Issue 7 https://doi.org/10.1021/jm0306430	journal	March 2004
Update of the CHARMM All-Atom Additive Force Field for Lipids: Validation on Six Lipid Types Klauda, Jeffery B.; Venable, Richard M.; Freites, J. Alfredo The Journal of Physical Chemistry B, Vol. 114, Issue 23 https://doi.org/10.1021/jp101759q	journal	June 2010
All-Atom Empirical Potential for Molecular Modeling and Dynamics Studies of Proteins ^† MacKerell, A. D.; Bashford, D.; Bellott, M. The Journal of Physical Chemistry B, Vol. 102, Issue 18 https://doi.org/10.1021/jp973084f	journal	April 1998
Structural insights into µ-opioid receptor activation Huang, Weijiao; Manglik, Aashish; Venkatakrishnan, A. J. Nature, Vol. 524, Issue 7565 https://doi.org/10.1038/nature14886	journal	August 2015
CHARMM36m: an improved force field for folded and intrinsically disordered proteins Huang, Jing; Rauscher, Sarah; Nawrocki, Grzegorz Nature Methods, Vol. 14, Issue 1 https://doi.org/10.1038/nmeth.4067	journal	November 2016
How μ-opioid receptor recognizes fentanyl Vo, Quynh N.; Mahinthichaichan, Paween; Shen, Jana Nature Communications, Vol. 12, Issue 1 https://doi.org/10.1038/s41467-021-21262-9	journal	February 2021
Comparison of simple potential functions for simulating liquid water Jorgensen, William L.; Chandrasekhar, Jayaraman; Madura, Jeffry D. The Journal of Chemical Physics, Vol. 79, Issue 2 https://doi.org/10.1063/1.445869	journal	July 1983
Finite representation of an infinite bulk system: Solvent boundary potential for computer simulations Beglov, Dmitrii; Roux, Benoît The Journal of Chemical Physics, Vol. 100, Issue 12 https://doi.org/10.1063/1.466711	journal	June 1994
OPM database and PPM web server: resources for positioning of proteins in membranes Lomize, Mikhail A.; Pogozheva, Irina D.; Joo, Hyeon Nucleic Acids Research, Vol. 40, Issue D1 https://doi.org/10.1093/nar/gkr703	journal	September 2011
Well-Tempered Metadynamics: A Smoothly Converging and Tunable Free-Energy Method Barducci, Alessandro; Bussi, Giovanni; Parrinello, Michele Physical Review Letters, Vol. 100, Issue 2 https://doi.org/10.1103/PhysRevLett.100.020603	journal	January 2008
Pharmacologic Characterization of Substituted Nitazenes at μ, κ, and Δ Opioid Receptors Suggests High Potential for Toxicity Kozell, Laura B.; Eshleman, Amy J.; Wolfrum, Katherine M. The Journal of Pharmacology and Experimental Therapeutics, Vol. 389, Issue 2 https://doi.org/10.1124/jpet.123.002052	journal	May 2024
Reanalysis of a μ opioid receptor crystal structure reveals a covalent adduct with BU72 Munro, Thomas A. BMC Biology, Vol. 21, Issue 1 https://doi.org/10.1186/s12915-023-01689-w	journal	October 2023
Chemical Genomics Profiling of Environmental Chemical Modulation of Human Nuclear Receptors Huang, Ruili; Xia, Menghang; Cho, Ming-Hsuang Environmental Health Perspectives, Vol. 119, Issue 8 https://doi.org/10.1289/ehp.1002952	journal	August 2011
OpenMM 7: Rapid development of high performance algorithms for molecular dynamics Eastman, Peter; Swails, Jason; Chodera, John D. PLOS Computational Biology, Vol. 13, Issue 7 https://doi.org/10.1371/journal.pcbi.1005659	journal	July 2017
Predicting opioid receptor binding affinity of pharmacologically unclassified designer substances using molecular docking Ellis, Christopher R.; Kruhlak, Naomi L.; Kim, Marlene T. PLOS ONE, Vol. 13, Issue 5 https://doi.org/10.1371/journal.pone.0197734	journal	May 2018
Analysis of the Results of Metadynamics Simulations by metadynminer and metadynminer3d Trapl, Dalibor; Spiwok, Vojtech The R Journal, Vol. 14, Issue 3 https://doi.org/10.32614/RJ-2022-057	journal	December 2022

Similar Records

Kinetics and Mechanism of Fentanyl Dissociation from the μ-Opioid Receptor

Journal Article · 2021 · JACS Au · OSTI ID:1829124

Mahinthichaichan, Paween; Vo, Quynh N.; Ellis, Christopher R.; +1 more

How μ-opioid receptor recognizes fentanyl

Journal Article · 2021 · Nature Communications · OSTI ID:1765423

Vo, Quynh N.; Mahinthichaichan, Paween; Shen, Jana; +1 more

Human Mu Opioid Receptor (OPRM1A118G) polymorphism is associated with brain mu- opioid receptor binding potential in smokers

Journal Article · 2011 · Proceedings of the National Academy of Sciences of the United States of America · OSTI ID:1040468

Ray, R; Logan, J; Ray, R; +9 more

Title: A putative binding model of nitazene derivatives at the μ-opioid receptor

Citation Formats

References (47)

Similar Records

Related Subjects