000884080 001__ 884080
000884080 005__ 20220930130250.0
000884080 0247_ $$2doi$$a10.1021/acs.jpclett.0c00999
000884080 0247_ $$2Handle$$a2128/25667
000884080 0247_ $$2altmetric$$aaltmetric:85998985
000884080 0247_ $$2pmid$$apmid:32672983
000884080 0247_ $$2WOS$$aWOS:000562064500081
000884080 037__ $$aFZJ-2020-03081
000884080 082__ $$a530
000884080 1001_ $$0P:(DE-Juel1)174546$$aCapelli, Riccardo$$b0$$eCorresponding author
000884080 245__ $$aAccuracy of Molecular Simulation-Based Predictions of k off Values: A Metadynamics Study
000884080 260__ $$aWashington, DC$$bACS$$c2020
000884080 3367_ $$2DRIVER$$aarticle
000884080 3367_ $$2DataCite$$aOutput Types/Journal article
000884080 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1605535180_2431
000884080 3367_ $$2BibTeX$$aARTICLE
000884080 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000884080 3367_ $$00$$2EndNote$$aJournal Article
000884080 520__ $$aThe koff values of ligands unbinding to proteins are key parameters for drug discovery. Their predictions based on molecular simulation may under- or overestimate experiment in a system- and/or technique-dependent way. Here we use an established method—infrequent metadynamics, based on the AMBER force field—to compute the koff of the ligand iperoxo (in clinical use) targeting the muscarinic receptor M2. The ligand charges are calculated by either (i) the Amber standard procedure or (ii) B3LYP-DFT. The calculations using (i) turn out not to provide a reasonable estimation of the transition-state free energy. Those using (ii) differ from experiment by 2 orders of magnitude. On the basis of B3LYP DFT QM/MM simulations, we suggest that the observed discrepancy in (ii) arises, at least in part, from the lack of electronic polarization and/or charge transfer in biomolecular force fields. These issues might be present in other systems, such as DNA–protein complexes.
000884080 536__ $$0G:(DE-HGF)POF3-574$$a574 - Theory, modelling and simulation (POF3-574)$$cPOF3-574$$fPOF III$$x0
000884080 536__ $$0G:(DE-Juel1)jias5d_20181101$$aHPC-aided design of drugs with improved kinetics of binding (jias5d_20181101)$$cjias5d_20181101$$fHPC-aided design of drugs with improved kinetics of binding$$x1
000884080 588__ $$aDataset connected to CrossRef
000884080 7001_ $$0P:(DE-Juel1)180596$$aLyu, Wenping$$b1$$ufzj
000884080 7001_ $$0P:(DE-Juel1)168432$$aBolnykh, Viacheslav$$b2
000884080 7001_ $$00000-0002-3925-3799$$aMeloni, Simone$$b3
000884080 7001_ $$00000-0001-7487-944X$$aOlsen, Jógvan Magnus Haugaard$$b4
000884080 7001_ $$00000-0002-1704-8591$$aRothlisberger, Ursula$$b5
000884080 7001_ $$0P:(DE-HGF)0$$aParrinello, Michele$$b6
000884080 7001_ $$0P:(DE-Juel1)145614$$aCarloni, Paolo$$b7
000884080 773__ $$0PERI:(DE-600)2522838-9$$a10.1021/acs.jpclett.0c00999$$gVol. 11, no. 15, p. 6373 - 6381$$n15$$p6373 - 6381$$tThe journal of physical chemistry letters$$v11$$x1948-7185$$y2020
000884080 8564_ $$uhttps://juser.fz-juelich.de/record/884080/files/Invoice.pdf
000884080 8564_ $$uhttps://juser.fz-juelich.de/record/884080/files/Invoice.pdf?subformat=pdfa$$xpdfa
000884080 8564_ $$uhttps://juser.fz-juelich.de/record/884080/files/Authors%27%20last%20version.pdf$$yPublished on 2020-07-16. Available in OpenAccess from 2021-07-16.$$zStatID:(DE-HGF)0510
000884080 8564_ $$uhttps://juser.fz-juelich.de/record/884080/files/Authors%27%20last%20version.pdf?subformat=pdfa$$xpdfa$$yPublished on 2020-07-16. Available in OpenAccess from 2021-07-16.$$zStatID:(DE-HGF)0510
000884080 8767_ $$8APC600161806$$92020-10-23$$d2020-10-23$$eHybrid-OA$$jStorniert$$zRechnung soll gesplittet werden, Frau Schulte kümmert sich, Order 10000211440, 3500.00 USD
000884080 8767_ $$8APC600161806A$$92020-10-23$$d2020-11-06$$eHybrid-OA$$jZahlung erfolgt$$z2625 USD Belegnr. 1200159313
000884080 8767_ $$8APC600161806$$92020-10-23$$d2020-10-23$$eHybrid-OA$$jZahlung angewiesen
000884080 909CO $$ooai:juser.fz-juelich.de:884080$$popenCost$$pVDB$$pdriver$$pOpenAPC$$popen_access$$popenaire$$pdnbdelivery
000884080 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)174546$$aForschungszentrum Jülich$$b0$$kFZJ
000884080 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)180596$$aForschungszentrum Jülich$$b1$$kFZJ
000884080 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)168432$$aForschungszentrum Jülich$$b2$$kFZJ
000884080 9101_ $$0I:(DE-HGF)0$$60000-0002-3925-3799$$aExternal Institute$$b3$$kExtern
000884080 9101_ $$0I:(DE-HGF)0$$60000-0001-7487-944X$$aExternal Institute$$b4$$kExtern
000884080 9101_ $$0I:(DE-HGF)0$$60000-0002-1704-8591$$aExternal Institute$$b5$$kExtern
000884080 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$aExternal Institute$$b6$$kExtern
000884080 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)145614$$aForschungszentrum Jülich$$b7$$kFZJ
000884080 9131_ $$0G:(DE-HGF)POF3-574$$1G:(DE-HGF)POF3-570$$2G:(DE-HGF)POF3-500$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bKey Technologies$$lDecoding the Human Brain$$vTheory, modelling and simulation$$x0
000884080 9141_ $$y2020
000884080 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2019-12-21
000884080 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2019-12-21
000884080 915__ $$0StatID:(DE-HGF)0530$$2StatID$$aEmbargoed OpenAccess
000884080 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bJ PHYS CHEM LETT : 2018$$d2019-12-21
000884080 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bJ PHYS CHEM LETT : 2018$$d2019-12-21
000884080 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2019-12-21
000884080 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index$$d2019-12-21
000884080 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2019-12-21
000884080 915__ $$0StatID:(DE-HGF)1150$$2StatID$$aDBCoverage$$bCurrent Contents - Physical, Chemical and Earth Sciences$$d2019-12-21
000884080 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database$$d2019-12-21
000884080 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2019-12-21
000884080 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2019-12-21
000884080 920__ $$lyes
000884080 9201_ $$0I:(DE-Juel1)IAS-5-20120330$$kIAS-5$$lComputational Biomedicine$$x0
000884080 9201_ $$0I:(DE-Juel1)INM-9-20140121$$kINM-9$$lComputational Biomedicine$$x1
000884080 9201_ $$0I:(DE-82)080012_20140620$$kJARA-HPC$$lJARA - HPC$$x2
000884080 980__ $$ajournal
000884080 980__ $$aVDB
000884080 980__ $$aI:(DE-Juel1)IAS-5-20120330
000884080 980__ $$aI:(DE-Juel1)INM-9-20140121
000884080 980__ $$aI:(DE-82)080012_20140620
000884080 980__ $$aAPC
000884080 980__ $$aUNRESTRICTED
000884080 9801_ $$aAPC
000884080 9801_ $$aFullTexts