{"doi":"10.1016/j.tips.2025.03.004","title":"The structural and functional dynamics of BiP and Grp94: opportunities for therapeutic discovery","abstract":null,"journal":"Trends in Pharmacological Sciences","year":2025,"id":612870,"datarank":0.3596842909197557,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"self_citation_contribution":0.3596842909197557,"citation_network_contribution":0.0,"self_endowment_contribution":0.3596842909197557,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"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":1578230,"name":"Chioma C. Ndolo","orcid":null,"position":1,"is_corresponding":false},{"id":1578231,"name":"Ayodeji A. Adedeji","orcid":null,"position":2,"is_corresponding":false},{"id":1578232,"name":"Hannah O. Popoola","orcid":null,"position":3,"is_corresponding":false},{"id":693775,"name":"Andrea N. Kravats","orcid":"0000-0001-8930-0170","position":4,"is_corresponding":false},{"id":1064868,"name":"Ikponwmosa Obaseki","orcid":"0000-0003-2280-9209","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The structural and functional dynamics of BiP and Grp94: opportunities for therapeutic discovery","abstract":"Binding immunoglobulin protein (BiP) and glucose-regulated protein 94 (Grp94) are endoplasmic reticulum (ER)-localized molecular chaperones that ensure proper protein folding and maintain protein homeostasis. However, overexpression of these chaperones during ER stress can contribute to disease progression in numerous pathologies. Although these chaperones represent promising therapeutic targets, their inhibition has been challenged by gaps in understanding of targetable chaperone features and their complex biology. To overcome these challenges, a new assay has been developed to selectively target BiP, and compounds that exploit subtle conformational changes of Grp94 have been designed. This review summarizes recent advances in elucidating structural and functional dynamics of BiP and Grp94. We explore leveraging this information to develop novel therapeutic interventions. Finally, given the recent advances in computing, we discuss how machine learning methods can be used to accelerate drug discovery efforts.","is_dataset_classified":null,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40253284","pmcid":"PMC12049254","openalex_id":"https://openalex.org/W4409588037","authors":[],"funders":[{"funder_name":"NIGMS NIH HHS","grant_id":"R35 GM146963","title":null}],"total_grants":1,"fwci":4.9316,"citation_percentile":0.95641156,"influential_citations":0,"citation_trend":[{"year":2025,"count":3},{"year":2026,"count":5}],"oa_status":"green","license":"http://www.elsevier.com/open-access/userlicense/1.0/","oa_locations":[{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12049254/","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12049254/","host_type":"repository"},{"url":"https://api.elsevier.com/content/article/PII:S0165614725000446?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0165614725000446?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.tips.2025.03.004","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40253284","host_type":"repository"}],"fields_of_study":["Endoplasmic Reticulum Stress and Disease","ATP Synthase and ATPases Research","Nuclear Structure and Function"],"mesh_terms":["Machine Learning","Endoplasmic Reticulum Chaperone BiP","Animals","Heat-Shock Proteins","Humans","Membrane Glycoproteins","Protein Conformation","HSP70 Heat-Shock Proteins","Drug Discovery"],"keywords":["Dynamics (music)","Computational biology","Neuroscience","Psychology","Cognitive science","Biology","Drug design","Molecular chaperones","GRP94","endoplasmic reticulum stress","Bip"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-02T05:20:02.900563Z","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":[]}