{"doi":"10.1016/j.xphs.2016.01.004","title":"Relating Protein–Protein Interactions and Aggregation Rates From Low to High Concentrations","abstract":null,"journal":"Journal of Pharmaceutical Sciences","year":2016,"id":616310,"datarank":0.6628260911694899,"base_score":4.418840607796598,"endowment":4.418840607796598,"self_citation_contribution":0.6628260911694899,"citation_network_contribution":0.0,"self_endowment_contribution":0.6628260911694899,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":82,"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":1588868,"name":"Cesar Calero-Rubio","orcid":null,"position":1,"is_corresponding":false},{"id":1588869,"name":"Atul Saluja","orcid":null,"position":2,"is_corresponding":false},{"id":216526,"name":"Christopher J. Roberts","orcid":null,"position":3,"is_corresponding":false},{"id":1588866,"name":"Ranendu Ghosh","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Relating Protein–Protein Interactions and Aggregation Rates From Low to High Concentrations","abstract":"At low protein concentrations (c2), non-native protein aggregation rates are known to be sensitive to changes in conformational stability and \"weak\" or \"colloidal\" protein-protein interactions. Protein-protein interactions are also known to be strong functions of c2. In the present work, protein-protein interactions and rates of aggregation were quantified systematically for a monoclonal antibody (MAb) across a broad range of c2 at pH 5.1 and 6.5, with or without 5 wt/wt % sucrose or 100 mM NaCl present. Aggregation rates were determined from initial-rate analysis with size-exclusion chromatography, and interactions were quantified with static and dynamic laser light scattering. A number of hypotheses were tested regarding whether changes in protein-protein interactions can be predictive of changes in aggregation rates versus c2. Hypotheses were based on (i) changes in thermodynamic activity; (ii) statistical mechanical fluctuation theory; and (iii) surface-contact probabilities. Arguments based on (i) and (ii) were qualitatively inconsistent with experimental rates and scattering. Hypothesis (iii) was reasonably successful and resulted in a semiquantitative correlation between rates and protein-protein interactions across almost 2 orders of magnitude in c2. However, (iii) requires one to assume that the concentration-dependent protein-protein Kirkwood-Buff integral is a reasonable surrogate for contact probabilities.","is_dataset_classified":null,"base_score":4.418840607796598,"endowment":4.418840607796598,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"26928400","pmcid":null,"openalex_id":"https://openalex.org/W2282215280","authors":[],"funders":[],"total_grants":0,"fwci":8.0174,"citation_percentile":0.97983768,"influential_citations":0,"citation_trend":[{"year":2016,"count":4},{"year":2017,"count":8},{"year":2018,"count":24},{"year":2019,"count":14},{"year":2020,"count":6},{"year":2021,"count":7},{"year":2022,"count":4},{"year":2023,"count":2},{"year":2024,"count":7},{"year":2025,"count":4},{"year":2026,"count":2}],"oa_status":"closed","license":"https://www.elsevier.com/tdm/userlicense/1.0/","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S0022354916002677?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0022354916002677?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.xphs.2016.01.004","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/26928400","host_type":"repository"}],"fields_of_study":["Protein purification and stability","Viral Infectious Diseases and Gene Expression in Insects","Monoclonal and Polyclonal Antibodies Research","Antibodies, Monoclonal","Chromatography, Gel","Dynamic Light Scattering","Hydrogen-Ion Concentration","Light","Protein Aggregates","Protein Conformation","Protein Interaction Domains and Motifs","Proteins","Thermodynamics"],"mesh_terms":["Dynamic Light Scattering","Antibodies, Monoclonal","Chromatography, Gel","Hydrogen-Ion Concentration","Light","Protein Conformation","Proteins","Thermodynamics","Protein Interaction Domains and Motifs","Protein Aggregates"],"keywords":["Protein aggregation","Chemistry","Size-exclusion chromatography","Protein–protein interaction","Protein stability","Dynamic light scattering","Colloid","Biophysics","Biochemistry","Nanoparticle","Materials science","Physical chemistry","Biology","Enzyme","Nanotechnology","Biotechnology","Biophysical Models","Protein Formulation","Light Scattering (Dynamic)"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Reduced inequalities"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-02T22:32:50.359496Z","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":[]}