Challenges in describing the conformation and dynamics of proteins with ambiguous behavior
Traditionally, our understanding of how proteins operate and how evolution shapes them is based on two main data sources: the overall protein fold and the protein amino acid sequence. However, a significant part of the proteome shows highly dynamic and/or structurally ambiguous behavior, which canno...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2022.959956/full |
| _version_ | 1818507689010921472 |
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| author | Joel Roca-Martinez Joel Roca-Martinez Tamas Lazar Tamas Lazar Jose Gavalda-Garcia Jose Gavalda-Garcia David Bickel David Bickel Rita Pancsa Bhawna Dixit Bhawna Dixit Bhawna Dixit Konstantina Tzavella Konstantina Tzavella Pathmanaban Ramasamy Pathmanaban Ramasamy Pathmanaban Ramasamy Maite Sanchez-Fornaris Maite Sanchez-Fornaris Maite Sanchez-Fornaris Isel Grau Wim F. Vranken Wim F. Vranken |
| author_facet | Joel Roca-Martinez Joel Roca-Martinez Tamas Lazar Tamas Lazar Jose Gavalda-Garcia Jose Gavalda-Garcia David Bickel David Bickel Rita Pancsa Bhawna Dixit Bhawna Dixit Bhawna Dixit Konstantina Tzavella Konstantina Tzavella Pathmanaban Ramasamy Pathmanaban Ramasamy Pathmanaban Ramasamy Maite Sanchez-Fornaris Maite Sanchez-Fornaris Maite Sanchez-Fornaris Isel Grau Wim F. Vranken Wim F. Vranken |
| author_sort | Joel Roca-Martinez |
| collection | DOAJ |
| description | Traditionally, our understanding of how proteins operate and how evolution shapes them is based on two main data sources: the overall protein fold and the protein amino acid sequence. However, a significant part of the proteome shows highly dynamic and/or structurally ambiguous behavior, which cannot be correctly represented by the traditional fixed set of static coordinates. Representing such protein behaviors remains challenging and necessarily involves a complex interpretation of conformational states, including probabilistic descriptions. Relating protein dynamics and multiple conformations to their function as well as their physiological context (e.g., post-translational modifications and subcellular localization), therefore, remains elusive for much of the proteome, with studies to investigate the effect of protein dynamics relying heavily on computational models. We here investigate the possibility of delineating three classes of protein conformational behavior: order, disorder, and ambiguity. These definitions are explored based on three different datasets, using interpretable machine learning from a set of features, from AlphaFold2 to sequence-based predictions, to understand the overlap and differences between these datasets. This forms the basis for a discussion on the current limitations in describing the behavior of dynamic and ambiguous proteins. |
| first_indexed | 2024-12-10T22:21:34Z |
| format | Article |
| id | doaj.art-cb1cd7e3a07a4ee9b141fef663760725 |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-12-10T22:21:34Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-cb1cd7e3a07a4ee9b141fef6637607252022-12-22T01:31:18ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2022-08-01910.3389/fmolb.2022.959956959956Challenges in describing the conformation and dynamics of proteins with ambiguous behaviorJoel Roca-Martinez0Joel Roca-Martinez1Tamas Lazar2Tamas Lazar3Jose Gavalda-Garcia4Jose Gavalda-Garcia5David Bickel6David Bickel7Rita Pancsa8Bhawna Dixit9Bhawna Dixit10Bhawna Dixit11Konstantina Tzavella12Konstantina Tzavella13Pathmanaban Ramasamy14Pathmanaban Ramasamy15Pathmanaban Ramasamy16Maite Sanchez-Fornaris17Maite Sanchez-Fornaris18Maite Sanchez-Fornaris19Isel Grau20Wim F. Vranken21Wim F. Vranken22Structural Biology Brussels, Vrije Universiteit Brussel, Brussels, BelgiumInteruniversity Institute of Bioinformatics in Brussels, VUB/ULB, Brussels, BelgiumStructural Biology Brussels, Vrije Universiteit Brussel, Brussels, BelgiumVIB-VUB Center for Structural Biology, Brussels, BelgiumStructural Biology Brussels, Vrije Universiteit Brussel, Brussels, BelgiumInteruniversity Institute of Bioinformatics in Brussels, VUB/ULB, Brussels, BelgiumStructural Biology Brussels, Vrije Universiteit Brussel, Brussels, BelgiumInteruniversity Institute of Bioinformatics in Brussels, VUB/ULB, Brussels, BelgiumResearch Centre for Natural Sciences, Institute of Enzymology, Budapest, HungaryStructural Biology Brussels, Vrije Universiteit Brussel, Brussels, BelgiumInteruniversity Institute of Bioinformatics in Brussels, VUB/ULB, Brussels, BelgiumIBiTech-Biommeda, Universiteit Gent, Gent, BelgiumStructural Biology Brussels, Vrije Universiteit Brussel, Brussels, BelgiumInteruniversity Institute of Bioinformatics in Brussels, VUB/ULB, Brussels, BelgiumStructural Biology Brussels, Vrije Universiteit Brussel, Brussels, BelgiumInteruniversity Institute of Bioinformatics in Brussels, VUB/ULB, Brussels, BelgiumVIB-UGent Center for Medical Biotechnology, Universiteit Gent, Gent, BelgiumStructural Biology Brussels, Vrije Universiteit Brussel, Brussels, BelgiumInteruniversity Institute of Bioinformatics in Brussels, VUB/ULB, Brussels, BelgiumDepartment of Computer Sciences, University of Camagüey, Camagüey, CubaInformation Systems, Eindhoven University of Technology, Eindhoven, NetherlandsStructural Biology Brussels, Vrije Universiteit Brussel, Brussels, BelgiumInteruniversity Institute of Bioinformatics in Brussels, VUB/ULB, Brussels, BelgiumTraditionally, our understanding of how proteins operate and how evolution shapes them is based on two main data sources: the overall protein fold and the protein amino acid sequence. However, a significant part of the proteome shows highly dynamic and/or structurally ambiguous behavior, which cannot be correctly represented by the traditional fixed set of static coordinates. Representing such protein behaviors remains challenging and necessarily involves a complex interpretation of conformational states, including probabilistic descriptions. Relating protein dynamics and multiple conformations to their function as well as their physiological context (e.g., post-translational modifications and subcellular localization), therefore, remains elusive for much of the proteome, with studies to investigate the effect of protein dynamics relying heavily on computational models. We here investigate the possibility of delineating three classes of protein conformational behavior: order, disorder, and ambiguity. These definitions are explored based on three different datasets, using interpretable machine learning from a set of features, from AlphaFold2 to sequence-based predictions, to understand the overlap and differences between these datasets. This forms the basis for a discussion on the current limitations in describing the behavior of dynamic and ambiguous proteins.https://www.frontiersin.org/articles/10.3389/fmolb.2022.959956/fullprotein dynamics and conformationsequence-based predictionbiophysical characteristicspost-translational modification (PTM)deleterious mutationfolding-upon-binding |
| spellingShingle | Joel Roca-Martinez Joel Roca-Martinez Tamas Lazar Tamas Lazar Jose Gavalda-Garcia Jose Gavalda-Garcia David Bickel David Bickel Rita Pancsa Bhawna Dixit Bhawna Dixit Bhawna Dixit Konstantina Tzavella Konstantina Tzavella Pathmanaban Ramasamy Pathmanaban Ramasamy Pathmanaban Ramasamy Maite Sanchez-Fornaris Maite Sanchez-Fornaris Maite Sanchez-Fornaris Isel Grau Wim F. Vranken Wim F. Vranken Challenges in describing the conformation and dynamics of proteins with ambiguous behavior Frontiers in Molecular Biosciences protein dynamics and conformation sequence-based prediction biophysical characteristics post-translational modification (PTM) deleterious mutation folding-upon-binding |
| title | Challenges in describing the conformation and dynamics of proteins with ambiguous behavior |
| title_full | Challenges in describing the conformation and dynamics of proteins with ambiguous behavior |
| title_fullStr | Challenges in describing the conformation and dynamics of proteins with ambiguous behavior |
| title_full_unstemmed | Challenges in describing the conformation and dynamics of proteins with ambiguous behavior |
| title_short | Challenges in describing the conformation and dynamics of proteins with ambiguous behavior |
| title_sort | challenges in describing the conformation and dynamics of proteins with ambiguous behavior |
| topic | protein dynamics and conformation sequence-based prediction biophysical characteristics post-translational modification (PTM) deleterious mutation folding-upon-binding |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2022.959956/full |
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