{"doi":"10.3389/fimmu.2018.00413","title":"Repertoire Analysis of Antibody CDR-H3 Loops Suggests Affinity Maturation Does Not Typically Result in Rigidification","abstract":null,"journal":"Frontiers in Immunology","year":2018,"id":593191,"datarank":2.0941331008660486,"base_score":4.204692619390966,"endowment":4.204692619390966,"self_citation_contribution":0.6307038929086449,"citation_network_contribution":1.4634292079574038,"self_endowment_contribution":0.6307038929086449,"citer_contribution":1.4634292079574038,"corpus_percentile":null,"corpus_rank":null,"citation_count":66,"citer_count":56,"citers_with_citation_signal":45,"citers_with_endowment":45,"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":1518231,"name":"Adnan Sljoka","orcid":null,"position":1,"is_corresponding":false},{"id":724178,"name":"Daisuke Kuroda","orcid":"0000-0003-2390-4785","position":2,"is_corresponding":false},{"id":1518232,"name":"Nobuyuki Tsuchimura","orcid":null,"position":3,"is_corresponding":false},{"id":1518233,"name":"Naoki Katoh","orcid":null,"position":4,"is_corresponding":false},{"id":724179,"name":"Kouhei Tsumoto","orcid":"0000-0001-7643-5164","position":5,"is_corresponding":false},{"id":242226,"name":"Jeffrey J. Gray","orcid":"0000-0001-6380-2324","position":6,"is_corresponding":false},{"id":567112,"name":"Jeliazko R. Jeliazkov","orcid":"0000-0003-4249-1955","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Repertoire Analysis of Antibody CDR-H3 Loops Suggests Affinity Maturation Does Not Typically Result in Rigidification","abstract":"Antibodies can rapidly evolve in specific response to antigens. Affinity maturation drives this evolution through cycles of mutation and selection leading to enhanced antibody specificity and affinity. Elucidating the biophysical mechanisms that underlie affinity maturation is fundamental to understanding B-cell immunity. An emergent hypothesis is that affinity maturation reduces the conformational flexibility of the antibody's antigen-binding paratope to minimize entropic losses incurred upon binding. In recent years, computational and experimental approaches have tested this hypothesis on a small number of antibodies, often observing a decrease in the flexibility of the complementarity determining region (CDR) loops that typically comprise the paratope and in particular the CDR-H3 loop, which contributes a plurality of antigen contacts. However, there were a few exceptions and previous studies were limited to a small handful of cases. Here, we determined the structural flexibility of the CDR-H3 loop for thousands of recent homology models of the human peripheral blood cell antibody repertoire using rigidity theory. We found no clear delineation in the flexibility of naïve and antigen-experienced antibodies. To account for possible sources of error, we additionally analyzed hundreds of human and mouse antibodies in the Protein Data Bank through both rigidity theory and B-factor analysis. By both metrics, we observed only a slight decrease in the CDR-H3 loop flexibility when comparing affinity matured antibodies to naïve antibodies, and the decrease was not as drastic as previously reported. Further analysis, incorporating molecular dynamics simulations, revealed a spectrum of changes in flexibility. Our results suggest that rigidification may be just one of many biophysical mechanisms for increasing affinity.","is_dataset_classified":null,"base_score":4.204692619390966,"endowment":4.204692619390966,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"29545810","pmcid":"PMC5840193","openalex_id":"https://openalex.org/W2949247256","authors":[],"funders":[{"funder_name":"National Institute of General Medical Sciences","grant_id":"F31-GM123616, R01-GM078221, T32-GM008403","title":null},{"funder_name":"Core Research for Evolutional Science and Technology","grant_id":"JPMJCR1402","title":null},{"funder_name":"Japan Society for the Promotion of Science","grant_id":"17K18113","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"T32 GM008403","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM078221","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"F31 GM123616","title":null},{"funder_name":"National Institutes of Health","grant_id":"5T32GM008403-22","title":"PROGRAM IN MOLECULAR BIOPHYSICS"},{"funder_name":"National Institutes of Health","grant_id":"2R01GM078221-06","title":"Prediction of the Structure of Therapeutic Antibodies with their Antigens"},{"funder_name":"National Institutes of Health","grant_id":"5F31GM123616-02","title":"Computational Design of Crystal Lattice Interactions to Determine Recalcitrant Protein Structures"},{"funder_name":"Natural Sciences and Engineering Research Council of Canada","grant_id":"unidentified","title":"unidentified"},{"funder_name":"Natural Sciences and Engineering Research Council of Canada","grant_id":"","title":null}],"total_grants":11,"fwci":2.2246,"citation_percentile":0.89188003,"influential_citations":0,"citation_trend":[{"year":2018,"count":4},{"year":2019,"count":12},{"year":2020,"count":7},{"year":2021,"count":4},{"year":2022,"count":6},{"year":2023,"count":6},{"year":2024,"count":9},{"year":2025,"count":11},{"year":2026,"count":7}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.3389/fimmu.2018.00413","host_type":"journal"},{"url":"https://doi.org/10.3389/fimmu.2018.00413","host_type":"publisher"},{"url":"http://journal.frontiersin.org/article/10.3389/fimmu.2018.00413/full","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/29545810","host_type":"repository"},{"url":"https://doaj.org/article/71ffaa1387714ac493a4968650387caa","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5840193","host_type":"repository"},{"url":"https://www.frontiersin.org/articles/10.3389/fimmu.2018.00413/pdf","host_type":"Unpaywall"},{"url":"https://europepmc.org/articles/PMC5840193","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC5840193?pdf=render","host_type":"Europe_PMC"},{"url":"https://doi.org/10.1101/230417","host_type":""},{"url":"http://dx.doi.org/10.3389/fimmu.2018.00413","host_type":""},{"url":"https://dx.doi.org/10.1101/230417","host_type":""},{"url":"https://dx.doi.org/10.3389/fimmu.2018.00413","host_type":""},{"url":"http://dx.doi.org/10.1101/230417","host_type":""}],"fields_of_study":["Glycosylation and Glycoproteins Research","Monoclonal and Polyclonal Antibodies Research","HER2/EGFR in Cancer Research","0301 basic medicine","03 medical and health sciences","0303 health sciences"],"mesh_terms":["Animals","Antibody Affinity","Antibody Specificity","Antigens","Binding Sites, Antibody","Humans","Immunoglobulin Heavy Chains","Immunologic Memory","Models, Chemical","Protein Conformation","Structure-Activity Relationship","Crystallography, X-Ray","Complementarity Determining Regions","Databases, Protein","Mice","Molecular Dynamics Simulation","Immunity, Humoral"],"keywords":["Repertoire","Antibody","Chemistry","Affinity maturation","Cell biology","Molecular biology","Biophysics","Biology","Computational biology","Immunology","Physics","Conformational flexibility","Molecular Dynamics Simulations","Complementarity Determining Regions","Rigidity Theory","Antibody Repertoires","Rosettaantibody","Pebble Game Algorithm","Protein Conformation","Antibody Affinity","Molecular Dynamics Simulation","Crystallography, X-Ray","Mice","Structure-Activity Relationship","Antibody Specificity","Animals","Humans","Antigens","Databases, Protein","RC581-607","Immunity, Humoral","Models, Chemical","Binding Sites, Antibody","Immunologic diseases. Allergy","Immunoglobulin Heavy Chains","Immunologic Memory"],"sdg_mappings":[{"sdg_number":7,"sdg_label":"7. Clean energy"},{"sdg_number":13,"sdg_label":"13. Climate action"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"pdb"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-26T17:42:33.561634Z","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":[]}