dc.contributor.author
Chen, Mingchen
dc.contributor.author
Chen, Xun
dc.contributor.author
Schafer, Nicholas P.
dc.contributor.author
Clementi, Cecilia
dc.contributor.author
Komives, Elizabeth A.
dc.contributor.author
Ferreiro, Diego U.
dc.contributor.author
Wolynes, Peter G.
dc.date.accessioned
2021-03-17T09:49:12Z
dc.date.available
2021-03-17T09:49:12Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/29963
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-29705
dc.description.abstract
To function, biomolecules require sufficient specificity of interaction as well as stability to live in the cell while still being able to move. Thermodynamic stability of only a limited number of specific structures is important so as to prevent promiscuous interactions. The individual interactions in proteins, therefore, have evolved collectively to give funneled minimally frustrated landscapes but some strategic parts of biomolecular sequences located at specific sites in the structure have been selected to be frustrated in order to allow both motion and interaction with partners. We describe a framework efficiently to quantify and localize biomolecular frustration at atomic resolution by examining the statistics of the energy changes that occur when the local environment of a site is changed. The location of patches of highly frustrated interactions correlates with key biological locations needed for physiological function. At atomic resolution, it becomes possible to extend frustration analysis to protein-ligand complexes. At this resolution one sees that drug specificity is correlated with there being a minimally frustrated binding pocket leading to a funneled binding landscape. Atomistic frustration analysis provides a route for screening for more specific compounds for drug discovery.
en
dc.format.extent
9 Seiten
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
Computational biophysics
en
dc.subject
Drug discovery
en
dc.subject
Protein folding
en
dc.subject.ddc
500 Naturwissenschaften und Mathematik::530 Physik::530 Physik
dc.subject.ddc
500 Naturwissenschaften und Mathematik::570 Biowissenschaften; Biologie::572 Biochemie
dc.title
Surveying biomolecular frustration at atomic resolution
dc.type
Wissenschaftlicher Artikel
dc.identifier.sepid
80577
dcterms.bibliographicCitation.articlenumber
5944
dcterms.bibliographicCitation.doi
10.1038/s41467-020-19560-9
dcterms.bibliographicCitation.journaltitle
Nature communications
dcterms.bibliographicCitation.number
1
dcterms.bibliographicCitation.originalpublishername
Nature Publishing
dcterms.bibliographicCitation.originalpublisherplace
London
dcterms.bibliographicCitation.volume
11
dcterms.bibliographicCitation.url
http://www.nature.com/articles/s41467-020-19560-9
refubium.affiliation
Physik
refubium.affiliation.other
Institut für Theoretische Physik
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refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.isPartOf.eissn
2041-1723