Surveying biomolecular frustration at atomic resolution

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dc.citation.articleNumber5944
dc.citation.journalTitleNature Communications
dc.citation.volumeNumber11
dc.contributor.authorChen, Mingchen
dc.contributor.authorChen, Xun
dc.contributor.authorSchafer, Nicholas P.
dc.contributor.authorClementi, Cecilia
dc.contributor.authorKomives, Elizabeth A.
dc.contributor.authorFerreiro, Diego U.
dc.contributor.authorWolynes, Peter G.
dc.contributor.orgCenter for Theoretical Biological Physics
dc.date.accessioned2020-12-16T19:47:24Z
dc.date.available2020-12-16T19:47:24Z
dc.date.issued2020
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.
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.
dc.identifier.digitals41467-020-19560-9
dc.identifier.doihttps://doi.org/10.1038/s41467-020-19560-9
dc.identifier.urihttps://hdl.handle.net/1911/109744
dc.language.isoeng
dc.publisherSpringer Nature
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.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleSurveying biomolecular frustration at atomic resolution
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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