Starting structures and NMR and simulation relaxation data for the structural ensembles of Dengue protease NS2B/NS3pro

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dc.contributor.authorPeter Agback
dc.contributor.authorTatiana Agback
dc.contributor.authorDmitry Lesovoy
dc.contributor.authorXiao Han
dc.contributor.authorAlexander Lomzov
dc.contributor.authorRenhua Sun
dc.contributor.authorTatyana Sandalova
dc.contributor.authorVladislav Orekhov
dc.contributor.authorAdnane Achour
dc.date.accessioned2025-01-20T09:47:48Z
dc.date.available2025-01-20T09:47:48Z
dc.date.issued2023-11-29T16:25:40.912073Z
dc.descriptionThe dengue protease NS2B/NS3pro has been reported to adopt either an ‘open’ or a ‘closed’ conformation. We have developed a conformational filter that combines nuclear magnetic resonance (NMR) with molecular dynamics (MD) simulations to identify conformational ensembles that dominate in solution. Experimental values derived from relaxation parameters for the backbone and methyl side chains were compared with the corresponding back-calculated relaxation parameters of different conformational ensembles obtained from free MD simulations. Our results demonstrate a high prevalence for the ‘closed’ conformational ensemble while the ‘open’ conformation is absent, indicating that the latter conformation is most probably due to crystal contacts. Conversely, conformational ensembles in which the positioning of the co-factor NS2B results in a ‘partially’ open conformation, previously described in both MD simulations and X-ray studies, were identified by our conformational filter. Altogether, we believe that our approach allows for unambiguous identification of true conformational ensembles, an essential step for reliable drug discovery.en_EN
dc.descriptionDengueproteaset NS2B/NS3pro har rapporterats anta antingen en "öppen" eller en "stängd" konformation. Vi har utvecklat ett konformationsfilter som kombinerar kärnmagnetisk resonans (NMR) med molekylär dynamiska (MD)-simuleringar för att identifiera konformationella ensembler som dominerar i lösning. Experimentella värden härledda från relaxationsparametrar för ryggraden och metylsidokedjorna jämfördes med motsvarande beräknade relaxationsparametrar för olika konformationella ensembler erhållna från fria MD-simuleringar. Våra resultat visar en hög prevalens för den "slutna" konformationsensemblen medan den "öppna" konformationen är frånvarande, vilket indikerar att den senare konformationen troligen beror på kristallkontakter. Omvänt identifierades konformationella ensembler där positioneringen av kofaktorn NS2B resulterar i en "delvis" öppen konformation, som tidigare beskrivits i både MD-simuleringar och röntgenstudier, av vårt konformationsfilter. Sammantaget tror vi att vårt tillvägagångssätt möjliggör entydig identifiering av verkliga konformationella ensembler, ett viktigt steg för tillförlitlig läkemedelsupptäckt.sv_SE
dc.description.sponsorshipSwedish Foundation for Strategic Researchen_EN
dc.description.sponsorshipStiftelsen för strategisk forskningsv_SE
dc.description.sponsorshipSwedish Research Councilen_EN
dc.description.sponsorshipVetenskapsrådetsv_SE
dc.description.sponsorshipSwedish Cancer Societyen_EN
dc.description.sponsorshipCancerfondensv_SE
dc.description.sponsorshipSwedish Research Councilen_EN
dc.description.sponsorshipVetenskapsrådetsv_SE
dc.identifier.govdocSLU.molsci.2023.4.4..IÄ-12
dc.identifier.urihttps://doi.org/10.5878/5wea-fk76
dc.identifier.urihttps://doi.org/10.5878/mwbf-2f66
dc.identifier.urihttps://hdl.handle.net/20.500.12703/5489
dc.languageotheren_EN
dc.publisherSwedish National Data Serviceen_EN
dc.publisherSvensk Nationell Datatjänstsv_SE
dc.subjectBioinformatics (Computational Biology)en_EN
dc.subjectBioinformatik (beräkningsbiologi)sv_SE
dc.subjectOther Physics Topicsen_EN
dc.subjectAnnan fysiksv_SE
dc.subjectStructural Biologyen_EN
dc.subjectStrukturbiologisv_SE
dc.subjectComputer and Information Scienceen_EN
dc.subjectData- och informationsvetenskap (Datateknik)sv_SE
dc.subjectPhysical Sciencesen_EN
dc.subjectFysiksv_SE
dc.subjectBiological Sciencesen_EN
dc.subjectBiologisv_SE
dc.subjectNatural Sciencesen_EN
dc.subjectNaturvetenskapsv_SE
dc.subjectmechanicsen_EN
dc.subjectmekaniksv_SE
dc.subjectresonanceen_EN
dc.subjectmethods of analysisen_EN
dc.subjectanalysmetodersv_SE
dc.subjectphysicsen_EN
dc.subjectfysiksv_SE
dc.subjectmethodsen_EN
dc.subjectmetodersv_SE
dc.subjectnatural sciencesen_EN
dc.subjectnaturvetenskapersv_SE
dc.subjectsocietal objectsen_EN
dc.subjectsamhälleliga objektsv_SE
dc.subjectsciences (branches of science)en_EN
dc.subjectvetenskapsgrenarsv_SE
dc.subjectabstract objectsen_EN
dc.subjectabstrakta objektsv_SE
dc.subjectsystems of a societyen_EN
dc.subjectsamhälleliga systemsv_SE
dc.subjectobjectsen_EN
dc.subjectentitetersv_SE
dc.subjectsystemsen_EN
dc.subjectsystemsv_SE
dc.titleStarting structures and NMR and simulation relaxation data for the structural ensembles of Dengue protease NS2B/NS3proen_EN
dc.titleStartstrukturer och NMR- och simuleringsrelaxationsdata för de strukturella ensemblerna av Dengue-proteas NS2B/NS3prosv_SE
dc.typeDatasetsv_SE
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Starting structures and NMR and simulation relaxation data for the structural ensembles of Dengue protease NS2B NS3pro