{"doi":"10.1371/journal.pcbi.1003192","title":"On the Importance of Polar Interactions for Complexes Containing Intrinsically Disordered Proteins","abstract":null,"journal":"PLoS Computational Biology","year":2013,"id":680083,"datarank":0.637274286307404,"base_score":4.248495242049359,"endowment":4.248495242049359,"self_citation_contribution":0.637274286307404,"citation_network_contribution":0.0,"self_endowment_contribution":0.637274286307404,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":69,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1755825,"name":"Dokyun Na","orcid":"0000-0002-9107-7040","position":1,"is_corresponding":false},{"id":292664,"name":"Jörg Gsponer","orcid":"0000-0003-3672-6594","position":2,"is_corresponding":false},{"id":1776913,"name":"Eric T. C. Wong","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"On the Importance of Polar Interactions for Complexes Containing Intrinsically Disordered Proteins","abstract":"There is a growing recognition for the importance of proteins with large intrinsically disordered (ID) segments in cell signaling and regulation. ID segments in these proteins often harbor regions that mediate molecular recognition. Coupled folding and binding of the recognition regions has been proposed to confer high specificity to interactions involving ID segments. However, researchers recently questioned the origin of the interaction specificity of ID proteins because of the overrepresentation of hydrophobic residues in their interaction interfaces. Here, we focused on the role of polar and charged residues in interactions mediated by ID segments. Making use of the extended nature of most ID segments when in complex with globular proteins, we first identified large numbers of complexes between globular proteins and ID segments by using radius-of-gyration-based selection criteria. Consistent with previous studies, we found the interfaces of these complexes to be enriched in hydrophobic residues, and that these residues contribute significantly to the stability of the interaction interface. However, our analyses also show that polar interactions play a larger role in these complexes than in structured protein complexes. Computational alanine scanning and salt-bridge analysis indicate that interfaces in ID complexes are highly complementary with respect to electrostatics, more so than interfaces of globular proteins. Follow-up calculations of the electrostatic contributions to the free energy of binding uncovered significantly stronger Coulombic interactions in complexes harbouring ID segments than in structured protein complexes. However, they are counter-balanced by even higher polar-desolvation penalties. We propose that polar interactions are a key contributing factor to the observed high specificity of ID segment-mediated interactions.","is_dataset_classified":null,"base_score":4.248495242049359,"endowment":4.248495242049359,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"23990768","pmcid":"PMC3749945","openalex_id":"https://openalex.org/W1995750846","authors":[],"funders":[{"funder_name":"Natural Sciences and Engineering Research Council of Canada","grant_id":"unidentified","title":"unidentified"}],"total_grants":1,"fwci":3.2981,"citation_percentile":0.92735461,"influential_citations":0,"citation_trend":[{"year":2014,"count":10},{"year":2015,"count":10},{"year":2016,"count":4},{"year":2017,"count":2},{"year":2018,"count":8},{"year":2019,"count":12},{"year":2020,"count":2},{"year":2021,"count":3},{"year":2022,"count":7},{"year":2023,"count":1},{"year":2024,"count":3},{"year":2025,"count":4},{"year":2026,"count":3}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1003192&type=printable","host_type":"journal"},{"url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1003192&type=printable","host_type":"publisher"},{"url":"http://dx.plos.org/10.1371/journal.pcbi.1003192","host_type":"publisher"},{"url":"https://doi.org/10.1371/journal.pcbi.1003192","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/23990768","host_type":"repository"},{"url":"http://europepmc.org/articles/PMC3749945","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3749945","host_type":"repository"},{"url":"http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.786.412","host_type":""},{"url":"https://doaj.org/article/96e0c4aabc154de09cb0fd78b3e43a93","host_type":"repository"},{"url":"https://figshare.com/articles/dataset/_On_the_Importance_of_Polar_Interactions_for_Complexes_Containing_Intrinsically_Disordered_Proteins_/780109","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC3749945","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC3749945?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1371/journal.pcbi.1003192","host_type":""},{"url":"https://dx.doi.org/10.1371/journal.pcbi.1003192","host_type":""}],"fields_of_study":["Protein Structure and Dynamics","Enzyme Structure and Function","Mass Spectrometry Techniques and Applications","0301 basic medicine","0303 health sciences","03 medical and health sciences","Amino Acids","Computational Biology","Databases, Protein","Hydrogen Bonding","Hydrophobic and Hydrophilic Interactions","Intrinsically Disordered Proteins","Models, Chemical","Models, Molecular","Protein Binding","Reproducibility of Results","Sequence Alignment","Static Electricity","Thermodynamics"],"mesh_terms":["Amino Acids","Hydrogen Bonding","Models, Chemical","Models, Molecular","Protein Binding","Thermodynamics","Reproducibility of Results","Sequence Alignment","Computational Biology","Databases, Protein","Static Electricity","Hydrophobic and Hydrophilic Interactions","Intrinsically Disordered Proteins"],"keywords":["Globular protein","Intrinsically disordered proteins","Protein–protein interaction","Salt bridge","Polar","Alanine scanning","Static electricity","Radius of gyration","Molecular recognition","Biophysics","Electrostatics","Chemistry","Crystallography","Chemical physics","Plasma protein binding","Protein structure","Hydrophobic effect","Folding (DSP implementation)","Biology","Biochemistry","Mutant","Polymer","Physics","Molecule","Mutagenesis","Models, Molecular","QH301-705.5","Computational Biology","Reproducibility of Results","Hydrogen Bonding","Models, Chemical","Thermodynamics","Biology (General)","Amino Acids","Databases, Protein","Hydrophobic and Hydrophilic Interactions","Sequence Alignment","Research Article","Protein Binding"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"pdb"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T14:21:29.153590Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}