Surveying biomolecular frustration at atomic resolution

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dc.citation.articleNumber5944en_US
dc.citation.journalTitleNature Communicationsen_US
dc.citation.volumeNumber11en_US
dc.contributor.authorChen, Mingchenen_US
dc.contributor.authorChen, Xunen_US
dc.contributor.authorSchafer, Nicholas P.en_US
dc.contributor.authorClementi, Ceciliaen_US
dc.contributor.authorKomives, Elizabeth A.en_US
dc.contributor.authorFerreiro, Diego U.en_US
dc.contributor.authorWolynes, Peter G.en_US
dc.contributor.orgCenter for Theoretical Biological Physicsen_US
dc.date.accessioned2020-12-16T19:47:24Zen_US
dc.date.available2020-12-16T19:47:24Zen_US
dc.date.issued2020en_US
dc.description.abstractTo 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_US
dc.identifier.citationChen, Mingchen, Chen, Xun, Schafer, Nicholas P., et al.. "Surveying biomolecular frustration at atomic resolution." <i>Nature Communications,</i> 11, (2020) Springer Nature: https://doi.org/10.1038/s41467-020-19560-9.en_US
dc.identifier.digitals41467-020-19560-9en_US
dc.identifier.doihttps://doi.org/10.1038/s41467-020-19560-9en_US
dc.identifier.urihttps://hdl.handle.net/1911/109744en_US
dc.language.isoengen_US
dc.publisherSpringer Natureen_US
dc.rightsThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleSurveying biomolecular frustration at atomic resolutionen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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