Electronic Polarization at the Interface between the p53 Transactivation Domain and Two Binding Partners

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dc.contributor.authorCorrigan, Alexsandra N.en
dc.contributor.authorLemkul, Justin A.en
dc.date.accessioned2023-01-12T19:16:34Zen
dc.date.available2023-01-12T19:16:34Zen
dc.date.issued2022-07-07en
dc.date.updated2023-01-12T18:41:19Zen
dc.description.abstractIntrinsically disordered proteins (IDPs) are an abundant class of highly charged proteins that participate in numerous crucial biological processes, often in regulatory roles. IDPs do not have one major free energy minimum with a dominant structure, instead existing as conformational ensembles of multiple semistable conformations. p53 is a prototypical protein with disordered regions and binds to many structurally diverse partners, making it a useful model for exploring the role of electrostatic interactions at IDP binding interfaces. In this study, we used the Drude-2019 force field to simulate the p53 transactivation domain with two protein partners to probe the role of electrostatic interactions in IDP protein-protein interactions. We found that the Drude-2019 polarizable force field reasonably reproduced experimental chemical shifts of the p53 transactivation domain (TAD) in one complex for which these data are available. We also found that the proteins in these complexes displayed dipole response at specific residues of each protein and that residues primarily involved in binding showed a large percent change in dipole moment between the unbound and complexed states. Probing the role of electrostatic interactions in IDP binding can allow us greater fundamental understanding of these interactions and may help with targeting p53 or its partners for drug design.en
dc.description.versionAccepted versionen
dc.format.extentPages 4814-4827en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1021/acs.jpcb.2c02268en
dc.identifier.eissn1520-5207en
dc.identifier.issn1520-6106en
dc.identifier.issue26en
dc.identifier.orcidLemkul, Justin [0000-0001-6661-8653]en
dc.identifier.pmid35749260en
dc.identifier.urihttp://hdl.handle.net/10919/113150en
dc.identifier.volume126en
dc.language.isoenen
dc.publisherAmerican Chemical Societyen
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/35749260en
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subject1.1 Normal biological development and functioningen
dc.subject1 Underpinning researchen
dc.subjectGeneric health relevanceen
dc.subject.meshProtein Bindingen
dc.subject.meshElectronicsen
dc.subject.meshTumor Suppressor Protein p53en
dc.subject.meshTranscriptional Activationen
dc.subject.meshMolecular Dynamics Simulationen
dc.subject.meshIntrinsically Disordered Proteinsen
dc.titleElectronic Polarization at the Interface between the p53 Transactivation Domain and Two Binding Partnersen
dc.title.serialJournal of Physical Chemistry Ben
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherJournal Articleen
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciencesen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/Biochemistryen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/CALS T&R Facultyen

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