Blind testing of cross-linking/mass spectrometry hybrid methods in CASP11

Simple item page
dc.contributor.authorSchneider, Michael
dc.contributor.authorBelsom, Adam
dc.contributor.authorRappsilber, Juri
dc.contributor.authorBrock, Oliver
dc.date.accessioned2017-07-14T10:50:11Z
dc.date.available2017-07-14T10:50:11Z
dc.date.issued2016
dc.description.abstractHybrid approaches combine computational methods with experimental data. The information contained in the experimental data can be leveraged to probe the structure of proteins otherwise elusive to computational methods. Compared with computational methods, the structures produced by hybrid methods exhibit some degree of experimental validation. In spite of these advantages, most hybrid methods have not yet been validated in blind tests, hampering their development. Here, we describe the first blind test of a specific cross-link based hybrid method in CASP. This blind test was coordinated by the CASP organizers and utilized a novel, high-density cross-linking/mass-spectrometry (CLMS) approach that is able to collect high-density CLMS data in a matter of days. This experimental protocol was developed in the Rappsilber laboratory. This approach exploits the chemistry of a highly reactive, photoactivatable cross-linker to produce an order of magnitude more cross-links than homobifunctional cross-linkers. The Rappsilber laboratory generated experimental CLMS data based on this protocol, submitted the data to the CASP organizers which then released this data to the CASP11 prediction groups in a separate, CLMS assisted modeling experiment. We did not observe a clear improvement of assisted models, presumably because the properties of the CLMS data-uncertainty in cross-link identification and residue-residue assignment, and uneven distribution over the protein-were largely unknown to the prediction groups and their approaches were not yet tailored to this kind of data. We also suggest modifications to the CLMS-CASP experiment and discuss the importance of rigorous blind testing in the development of hybrid methods. (C) 2016 The Authors Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc.en
dc.identifier.eissn1097-0134
dc.identifier.issn0887-3585
dc.identifier.pmid26945814
dc.identifier.urihttps://depositonce.tu-berlin.de/handle/11303/6489
dc.identifier.urihttp://dx.doi.org/10.14279/depositonce-5997
dc.language.isoen
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subject.ddc570 Biowissenschaften; Biologiede
dc.subject.otherblind testen
dc.subject.otherhybrid methodsen
dc.subject.otherprotein structure predictionen
dc.subject.otherCASPen
dc.subject.othercross-linkingen
dc.subject.othermass spectrometryen
dc.titleBlind testing of cross-linking/mass spectrometry hybrid methods in CASP11en
dc.typeArticleen
dc.type.versionpublishedVersionen
dcterms.bibliographicCitation.doi10.1002/prot.25028
dcterms.bibliographicCitation.journaltitleProteins : structure, function, and bioinformaticsen
dcterms.bibliographicCitation.originalpublishernameWileyen
dcterms.bibliographicCitation.originalpublisherplaceHoboken, NJ [u.a.]en
dcterms.bibliographicCitation.pageend163
dcterms.bibliographicCitation.pagestart152
dcterms.bibliographicCitation.volume84
tub.accessrights.dnbfree
tub.affiliationFak. 3 Prozesswissenschaften::Inst. Biotechnologie::FG Bioanalytikde
tub.affiliationFak. 2 Mathematik und Naturwissenschaften::Inst. Festkörperphysik::FG Neue Materialiende
tub.affiliation.facultyFak. 3 Prozesswissenschaftende
tub.affiliation.facultyFak. 2 Mathematik und Naturwissenschaftende
tub.affiliation.groupFG Bioanalytikde
tub.affiliation.groupFG Neue Materialiende
tub.affiliation.instituteInst. Biotechnologiede
tub.affiliation.instituteInst. Festkörperphysikde
tub.publisher.universityorinstitutionTechnische Universität Berlin

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
10.1002.prot.25028.pdf
Size:
543.13 KB
Format:
Adobe Portable Document Format
Download

Collections

Publications