Solving protein structures using short-distance cross-linking constraints as a guide for discrete molecular dynamics simulations

dc.contributor.authorBrodie, Nicholas I.
dc.contributor.authorPopov, Konstantin I.
dc.contributor.authorPetrotchenko, Evgeniy V.
dc.contributor.authorDokholyan, Nikolay V.
dc.contributor.authorBorchers, Christoph H.
dc.date.accessioned2018-09-07T21:07:50Z
dc.date.available2018-09-07T21:07:50Z
dc.date.copyright2017en_US
dc.date.issued2017
dc.description.abstractWe present an integrated experimental and computational approach for de novo protein structure determination in which short-distance cross-linking data are incorporated into rapid discrete molecular dynamics (DMD) simulations as constraints, reducing the conformational space and achieving the correct protein folding on practical time scales. We tested our approach on myoglobin and FK506 binding protein—models for α helix–rich and β sheet–rich proteins, respectively—and found that the lowest-energy structures obtained were in agreement with the crystal structure, hydrogen-deuterium exchange, surface modification, and long-distance cross-linking validation data. Our approach is readily applicable to other proteins with unknown structures.en_US
dc.description.reviewstatusRevieweden_US
dc.description.scholarlevelFacultyen_US
dc.description.sponsorshipThe University of Victoria–Genome British Columbia Proteomics Centre was supported by the Genomic Innovations Network from Genome Canada and Genome British Columbia (project codes 204PRO and 214PRO). C.H.B. would also like to thank the Natural Sciences and Engineering Research Council of Canada and the Leading Edge Endowment Fund for support. This work was also supported by NIH grants R01GM080742, R01GM114015, R01GM081764, and R01GM123247.en_US
dc.identifier.citationBrodie, N.I.; Popov, K.I.; Petrotchenko, E.V.; Dokholyan, N.V.; & Borchers, C.H. (2017). Solving protein structures using short-distance cross-linking constraints as a guide for discrete molecular dynamics simulations. Science Advances, 3(7), e1700479. DOI: 10.1126/sciadv.1700479en_US
dc.identifier.urihttps://doi.org/10.1126/sciadv.1700479
dc.identifier.urihttp://hdl.handle.net/1828/10044
dc.language.isoenen_US
dc.publisherScience Advancesen_US
dc.titleSolving protein structures using short-distance cross-linking constraints as a guide for discrete molecular dynamics simulationsen_US
dc.typeArticleen_US

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