000858888 001__ 858888 000858888 005__ 20240625095120.0 000858888 0247_ $$2doi$$a10.1371/journal.pcbi.1006642 000858888 0247_ $$2ISSN$$a1553-734X 000858888 0247_ $$2ISSN$$a1553-7358 000858888 0247_ $$2Handle$$a2128/21501 000858888 0247_ $$2pmid$$apmid:30521520 000858888 0247_ $$2WOS$$aWOS:000454835100039 000858888 0247_ $$2altmetric$$aaltmetric:52319100 000858888 037__ $$aFZJ-2018-07724 000858888 082__ $$a610 000858888 1001_ $$0P:(DE-Juel1)169975$$aBochicchio, Anna$$b0$$eCorresponding author$$ufzj 000858888 245__ $$aMolecular basis for the increased affinity of an RNA recognition motif with re-engineered specificity: A molecular dynamics and enhanced sampling simulations study 000858888 260__ $$aSan Francisco, Calif.$$bPublic Library of Science$$c2018 000858888 3367_ $$2DRIVER$$aarticle 000858888 3367_ $$2DataCite$$aOutput Types/Journal article 000858888 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1674540630_28768 000858888 3367_ $$2BibTeX$$aARTICLE 000858888 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000858888 3367_ $$00$$2EndNote$$aJournal Article 000858888 520__ $$aThe RNA recognition motif (RRM) is the most common RNA binding domain across eukaryotic proteins. It is therefore of great value to engineer its specificity to target RNAs of arbitrary sequence. This was recently achieved for the RRM in Rbfox protein, where four mutations R118D, E147R, N151S, and E152T were designed to target the precursor to the oncogenic miRNA 21. Here, we used a variety of molecular dynamics-based approaches to predict specific interactions at the binding interface. Overall, we have run approximately 50 microseconds of enhanced sampling and plain molecular dynamics simulations on the engineered complex as well as on the wild-type Rbfox·pre-miRNA 20b from which the mutated systems were designed. Comparison with the available NMR data on the wild type molecules (protein, RNA, and their complex) served to establish the accuracy of the calculations.Free energy calculations suggest that further improvements in affinity and selectivity are achieved by the S151T replacement. 000858888 536__ $$0G:(DE-HGF)POF3-574$$a574 - Theory, modelling and simulation (POF3-574)$$cPOF3-574$$fPOF III$$x0 000858888 588__ $$aDataset connected to CrossRef 000858888 7001_ $$00000-0002-9833-4281$$aKrepl, Miroslav$$b1$$eCorresponding author 000858888 7001_ $$0P:(DE-HGF)0$$aYang, Fan$$b2 000858888 7001_ $$0P:(DE-HGF)0$$aVarani, Gabriele$$b3 000858888 7001_ $$00000-0001-6558-6186$$aSponer, Jiri$$b4 000858888 7001_ $$0P:(DE-Juel1)145614$$aCarloni, Paolo$$b5$$eCorresponding author$$ufzj 000858888 773__ $$0PERI:(DE-600)2193340-6$$a10.1371/journal.pcbi.1006642$$gVol. 14, no. 12, p. e1006642 -$$n12$$pe1006642 -$$tPLoS Computational Biology$$v14$$x1553-7358$$y2018 000858888 8564_ $$uhttps://juser.fz-juelich.de/record/858888/files/journal.pcbi.1006642.pdf$$yOpenAccess 000858888 8564_ $$uhttps://juser.fz-juelich.de/record/858888/files/journal.pcbi.1006642.pdf?subformat=pdfa$$xpdfa$$yOpenAccess 000858888 8767_ $$8PAB233524$$92018-12-02$$d2018-12-20$$eAPC$$jZahlung erfolgt$$lDeposit: PLoS$$pPCOMPBIOL-D-18-01097$$z2350 USD 000858888 909CO $$ooai:juser.fz-juelich.de:858888$$pdnbdelivery$$popenCost$$pVDB$$pdriver$$pOpenAPC$$popen_access$$popenaire 000858888 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)169975$$aForschungszentrum Jülich$$b0$$kFZJ 000858888 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)145614$$aForschungszentrum Jülich$$b5$$kFZJ 000858888 9131_ $$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$$x0 000858888 9141_ $$y2018 000858888 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS 000858888 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews 000858888 915__ $$0LIC:(DE-HGF)CCBY4$$2HGFVOC$$aCreative Commons Attribution CC BY 4.0 000858888 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search 000858888 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bPLOS COMPUT BIOL : 2017 000858888 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal 000858888 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ 000858888 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded 000858888 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection 000858888 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF < 5 000858888 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess 000858888 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC 000858888 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database 000858888 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline 000858888 915__ $$0StatID:(DE-HGF)0320$$2StatID$$aDBCoverage$$bPubMed Central 000858888 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List 000858888 920__ $$lyes 000858888 9201_ $$0I:(DE-Juel1)IAS-5-20120330$$kIAS-5$$lComputational Biomedicine$$x0 000858888 9201_ $$0I:(DE-Juel1)INM-11-20170113$$kINM-11$$lJara-Institut Quantum Information$$x1 000858888 9201_ $$0I:(DE-Juel1)INM-9-20140121$$kINM-9$$lComputational Biomedicine$$x2 000858888 980__ $$ajournal 000858888 980__ $$aVDB 000858888 980__ $$aI:(DE-Juel1)IAS-5-20120330 000858888 980__ $$aI:(DE-Juel1)INM-11-20170113 000858888 980__ $$aI:(DE-Juel1)INM-9-20140121 000858888 980__ $$aAPC 000858888 980__ $$aUNRESTRICTED 000858888 9801_ $$aAPC 000858888 9801_ $$aFullTexts