Generating a conformational landscape of ubiquitin chains at atomistic resolution by back-mapping based sampling

Lade...
Vorschaubild
Dateien
Hunkler_2-26fblw16qqrr8.pdf
Hunkler_2-26fblw16qqrr8.pdfGröße: 2.84 MBDownloads: 84
Datum
2023
Herausgeber:innen
Kontakt
ISSN der Zeitschrift
Electronic ISSN
ISBN
Bibliografische Daten
Verlag
Schriftenreihe
Auflagebezeichnung
ArXiv-ID
Internationale Patentnummer
Link zur Lizenz
Angaben zur Forschungsförderung
Projekt
Open Access-Veröffentlichung
Open Access Gold
Sammlungen
Core Facility der Universität Konstanz
Gesperrt bis
Titel in einer weiteren Sprache
Forschungsvorhaben
Organisationseinheiten
Zeitschriftenheft
Publikationstyp
Zeitschriftenartikel
Publikationsstatus
Published
Erschienen in
Frontiers in Chemistry. Frontiers Research Foundation. 2023, 10, 1087963. eISSN 2296-2646. Available under: doi: 10.3389/fchem.2022.1087963
Zusammenfassung

Ubiquitin chains are flexible multidomain proteins that have important biological functions in cellular signalling. Computational studies with all-atom molecular dynamics simulations of the conformational spaces of polyubiquitins can be challenging due to the system size and a multitude of long-lived meta-stable states. Coarse graining is an efficient approach to overcome this problem—at the cost of losing high-resolution details. Recently, we proposed the back-mapping based sampling (BMBS) approach that reintroduces atomistic information into a given coarse grained (CG) sampling based on a two-dimensional (2D) projection of the conformational landscape, produces an atomistic ensemble and allows to systematically compare the ensembles at the two levels of resolution. Here, we apply BMBS to K48-linked tri-ubiquitin, showing its applicability to larger systems than those it was originally introduced on and demonstrating that the algorithm scales very well with system size. In an extension of the original BMBS we test three different seeding strategies, i.e. different approaches from where in the CG landscape atomistic trajectories are initiated. Furthermore, we apply a recently introduced conformational clustering algorithm to the back-mapped atomistic ensemble. Thus, we obtain insight into the structural composition of the 2D landscape and illustrate that the dimensionality reduction algorithm separates different conformational characteristics very well into different regions of the map. This cluster analysis allows us to show how atomistic trajectories sample conformational states, move through the projection space and in sum converge to an atomistic conformational landscape that slightly differs from the original CG map, indicating a correction of flaws in the CG template.

Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
540 Chemie
Schlagwörter
molecular dynamics simulations, dimensionality reduction, back-mapping, coarse graining, clustering, ubiquitin, polyubiquitin
Konferenz
Rezension
undefined / . - undefined, undefined
Zitieren
ISO 690HUNKLER, Simon, Teresa BUHL, Oleksandra KUKHARENKO, Christine PETER, 2023. Generating a conformational landscape of ubiquitin chains at atomistic resolution by back-mapping based sampling. In: Frontiers in Chemistry. Frontiers Research Foundation. 2023, 10, 1087963. eISSN 2296-2646. Available under: doi: 10.3389/fchem.2022.1087963
BibTex
@article{Hunkler2023-01-10Gener-59951,
  year={2023},
  doi={10.3389/fchem.2022.1087963},
  title={Generating a conformational landscape of ubiquitin chains at atomistic resolution by back-mapping based sampling},
  volume={10},
  journal={Frontiers in Chemistry},
  author={Hunkler, Simon and Buhl, Teresa and Kukharenko, Oleksandra and Peter, Christine},
  note={DFG-Förderung: CRC 969, Grant INST 35/1134-1 FUGG Article Number: 1087963}
}
RDF
<rdf:RDF
    xmlns:dcterms="http://purl.org/dc/terms/"
    xmlns:dc="http://purl.org/dc/elements/1.1/"
    xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
    xmlns:bibo="http://purl.org/ontology/bibo/"
    xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#"
    xmlns:foaf="http://xmlns.com/foaf/0.1/"
    xmlns:void="http://rdfs.org/ns/void#"
    xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > 
  <rdf:Description rdf:about="https://kops.uni-konstanz.de/server/rdf/resource/123456789/59951">
    <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/59951"/>
    <dc:language>eng</dc:language>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2023-01-26T09:51:11Z</dcterms:available>
    <dcterms:abstract xml:lang="eng">Ubiquitin chains are flexible multidomain proteins that have important biological functions in cellular signalling. Computational studies with all-atom molecular dynamics simulations of the conformational spaces of polyubiquitins can be challenging due to the system size and a multitude of long-lived meta-stable states. Coarse graining is an efficient approach to overcome this problem—at the cost of losing high-resolution details. Recently, we proposed the back-mapping based sampling (BMBS) approach that reintroduces atomistic information into a given coarse grained (CG) sampling based on a two-dimensional (2D) projection of the conformational landscape, produces an atomistic ensemble and allows to systematically compare the ensembles at the two levels of resolution. Here, we apply BMBS to K48-linked tri-ubiquitin, showing its applicability to larger systems than those it was originally introduced on and demonstrating that the algorithm scales very well with system size. In an extension of the original BMBS we test three different seeding strategies, i.e. different approaches from where in the CG landscape atomistic trajectories are initiated. Furthermore, we apply a recently introduced conformational clustering algorithm to the back-mapped atomistic ensemble. Thus, we obtain insight into the structural composition of the 2D landscape and illustrate that the dimensionality reduction algorithm separates different conformational characteristics very well into different regions of the map. This cluster analysis allows us to show how atomistic trajectories sample conformational states, move through the projection space and in sum converge to an atomistic conformational landscape that slightly differs from the original CG map, indicating a correction of flaws in the CG template.</dcterms:abstract>
    <dc:rights>Attribution 4.0 International</dc:rights>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/29"/>
    <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/59951/1/Hunkler_2-26fblw16qqrr8.pdf"/>
    <dcterms:title>Generating a conformational landscape of ubiquitin chains at atomistic resolution by back-mapping based sampling</dcterms:title>
    <dc:contributor>Peter, Christine</dc:contributor>
    <dcterms:rights rdf:resource="http://creativecommons.org/licenses/by/4.0/"/>
    <dc:creator>Peter, Christine</dc:creator>
    <dc:creator>Buhl, Teresa</dc:creator>
    <dc:contributor>Hunkler, Simon</dc:contributor>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <dc:contributor>Kukharenko, Oleksandra</dc:contributor>
    <dc:contributor>Buhl, Teresa</dc:contributor>
    <dcterms:issued>2023-01-10</dcterms:issued>
    <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/59951/1/Hunkler_2-26fblw16qqrr8.pdf"/>
    <dc:creator>Hunkler, Simon</dc:creator>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/29"/>
    <dc:creator>Kukharenko, Oleksandra</dc:creator>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2023-01-26T09:51:11Z</dc:date>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
  </rdf:Description>
</rdf:RDF>
Interner Vermerk
xmlui.Submission.submit.DescribeStep.inputForms.label.kops_note_fromSubmitter
Kontakt
URL der Originalveröffentl.
Prüfdatum der URL
Prüfungsdatum der Dissertation
Finanzierungsart
Kommentar zur Publikation
DFG-Förderung: CRC 969, Grant INST 35/1134-1 FUGG
Allianzlizenz
Corresponding Authors der Uni Konstanz vorhanden
Internationale Co-Autor:innen
Universitätsbibliographie
Ja
Begutachtet
Ja
Link zu Forschungsdaten
Beschreibung der Forschungsdaten
Python notebooks used to analyze the data
CG trajectories, selected back-mapping points and encodermap projections of all used data
Diese Publikation teilen