Intrinsically disordered proteins: Ensembles at the limits of Anfinsen's dogma

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MetadadosDescriçãoIdioma
Autor(es): dc.contributorCity of Hope National Medical Center-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorIndian Institute of Science Education and Research Kolkata-
Autor(es): dc.contributorIndian Institute of Science-
Autor(es): dc.contributorNorth Carolina State University-
Autor(es): dc.contributorUniversity of Maryland Institute for Bioscience and Biotechnology Research-
Autor(es): dc.contributorUniversity of Maryl-
Autor(es): dc.contributorRice University-
Autor(es): dc.contributorUniversity of South Florida-
Autor(es): dc.contributorthe Russian Academy of Sciences-
Autor(es): dc.creatorKulkarni, Prakash-
Autor(es): dc.creatorLeite, Vitor B. P.-
Autor(es): dc.creatorRoy, Susmita-
Autor(es): dc.creatorBhattacharyya, Supriyo-
Autor(es): dc.creatorMohanty, Atish-
Autor(es): dc.creatorAchuthan, Srisairam-
Autor(es): dc.creatorSingh, Divyoj-
Autor(es): dc.creatorAppadurai, Rajeswari-
Autor(es): dc.creatorRangarajan, Govindan-
Autor(es): dc.creatorWeninger, Keith-
Autor(es): dc.creatorOrban, John-
Autor(es): dc.creatorSrivastava, Anand-
Autor(es): dc.creatorJolly, Mohit Kumar-
Autor(es): dc.creatorOnuchic, Jose N.-
Autor(es): dc.creatorUversky, Vladimir N.-
Autor(es): dc.creatorSalgia, Ravi-
Data de aceite: dc.date.accessioned2025-08-21T15:49:10Z-
Data de disponibilização: dc.date.available2025-08-21T15:49:10Z-
Data de envio: dc.date.issued2025-04-29-
Data de envio: dc.date.issued2022-03-01-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1063/5.0080512-
Fonte completa do material: dc.identifierhttps://hdl.handle.net/11449/301216-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/301216-
Descrição: dc.descriptionIntrinsically disordered proteins (IDPs) are proteins that lack rigid 3D structure. Hence, they are often misconceived to present a challenge to Anfinsen's dogma. However, IDPs exist as ensembles that sample a quasi-continuum of rapidly interconverting conformations and, as such, may represent proteins at the extreme limit of the Anfinsen postulate. IDPs play important biological roles and are key components of the cellular protein interaction network (PIN). Many IDPs can interconvert between disordered and ordered states as they bind to appropriate partners. Conformational dynamics of IDPs contribute to conformational noise in the cell. Thus, the dysregulation of IDPs contributes to increased noise and “promiscuous” interactions. This leads to PIN rewiring to output an appropriate response underscoring the critical role of IDPs in cellular decision making. Nonetheless, IDPs are not easily tractable experimentally. Furthermore, in the absence of a reference conformation, discerning the energy landscape representation of the weakly funneled IDPs in terms of reaction coordinates is challenging. To understand conformational dynamics in real time and decipher how IDPs recognize multiple binding partners with high specificity, several sophisticated knowledge-based and physics-based in silico sampling techniques have been developed. Here, using specific examples, we highlight recent advances in energy landscape visualization and molecular dynamics simulations to discern conformational dynamics and discuss how the conformational preferences of IDPs modulate their function, especially in phenotypic switching. Finally, we discuss recent progress in identifying small molecules targeting IDPs underscoring the potential therapeutic value of IDPs. Understanding structure and function of IDPs can not only provide new insight on cellular decision making but may also help to refine and extend Anfinsen's structure/function paradigm.-
Descrição: dc.descriptionDepartment of Medical Oncology and Therapeutics Research City of Hope National Medical Center-
Descrição: dc.descriptionDepartamento de Física Instituto de Biociências Letras e Ciências Exatas Universidade Estadual Paulista (UNESP), São José do Rio Preto-
Descrição: dc.descriptionDepartment of Chemical Sciences Indian Institute of Science Education and Research Kolkata, West Bengal-
Descrição: dc.descriptionTranslational Bioinformatics Center for Informatics Department of Computational and Quantitative Medicine City of Hope National Medical Center-
Descrição: dc.descriptionCenter for Informatics Division of Research Informatics City of Hope National Medical Center-
Descrição: dc.descriptionCenter for BioSystems Science and Engineering Indian Institute of Science-
Descrição: dc.descriptionMolecular Biophysics Unit Indian Institute of Science, Karnataka-
Descrição: dc.descriptionDepartment of Mathematics Indian Institute of Science-
Descrição: dc.descriptionDepartment of Physics North Carolina State University-
Descrição: dc.descriptionW. M. Keck Laboratory for Structural Biology University of Maryland Institute for Bioscience and Biotechnology Research-
Descrição: dc.descriptionDepartment of Chemistry and Biochemistry University of Maryl-
Descrição: dc.descriptionCenter for Theoretical Biological Physics Rice University-
Descrição: dc.descriptionDepartment of Molecular Medicine College of Medicine Byrd Alzheimer's Institute University of South Florida-
Descrição: dc.descriptionProtein Research Group Institute for Biological Instrumentation the Russian Academy of Sciences-
Descrição: dc.descriptionDepartamento de Física Instituto de Biociências Letras e Ciências Exatas Universidade Estadual Paulista (UNESP), São José do Rio Preto-
Idioma: dc.languageen-
Relação: dc.relationBiophysics Reviews-
???dc.source???: dc.sourceScopus-
Título: dc.titleIntrinsically disordered proteins: Ensembles at the limits of Anfinsen's dogma-
Tipo de arquivo: dc.typevídeo-
Aparece nas coleções:Repositório Institucional - Unesp

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