{"doi":"10.1073/pnas.1517288113","title":"Understanding TRPV1 activation by ligands: Insights from the binding modes of capsaicin and resiniferatoxin","abstract":"<jats:title>Significance</jats:title>\n          <jats:p>Using computational methodologies, we refined the binding modes of the transient receptor potential cation channel subfamily V member 1 (TRPV1) modulators, capsaicin and resiniferatoxin, provided by the recent experimental cryo-electron microscopy electron density. The resulting insights enable us to predict the binding pose of 96 additional TRPV1 agonists, which we compare with reported mutagenesis studies. Specifically, we characterize the response of five previously unidentified mutants to capsaicin and resiniferatoxin. Analysis of the amino acids engaged in favorable ligand–channel interactions defines the key structural determinants of the TRPV1 vanilloid binding site.</jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2016,"id":28563,"datarank":5.923135858490585,"base_score":5.14166355650266,"endowment":5.14166355650266,"self_citation_contribution":0.7712495334753992,"citation_network_contribution":5.151886325015186,"self_endowment_contribution":0.7712495334753992,"citer_contribution":5.151886325015186,"corpus_percentile":null,"corpus_rank":null,"citation_count":170,"citer_count":157,"citers_with_citation_signal":138,"citers_with_endowment":138,"datacite_reuse_total":2,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":159645,"name":"Phanindra Velisetty","orcid":null,"position":1,"is_corresponding":false},{"id":159646,"name":"Lucie Delemotte","orcid":null,"position":2,"is_corresponding":false},{"id":98186,"name":"Eugene Palovcak","orcid":"0009-0003-8297-6778","position":3,"is_corresponding":false},{"id":54646,"name":"Michael L. Klein","orcid":null,"position":4,"is_corresponding":false},{"id":153652,"name":"Tibor Rohacs","orcid":null,"position":5,"is_corresponding":false},{"id":159647,"name":"Vincenzo Carnevale","orcid":null,"position":6,"is_corresponding":false},{"id":159644,"name":"Khaled Elokely","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":5.14166355650266,"endowment":5.14166355650266,"datacite_reuse_total":2,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"26719417","pmcid":null,"openalex_id":"https://openalex.org/W2212776737","authors":[],"funders":[{"funder_name":"HHS | NIH | National Institute of General Medical Sciences","grant_id":"P01 GM55876","title":null},{"funder_name":"NSF | CISE | Advanced Cyberinfrastructure","grant_id":"ACI-1440059","title":null},{"funder_name":"European Union Seventh Framework Program","grant_id":"PIOF-GA-2012-329534","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01GM093290","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"P01 GM055876","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"R01 NS055159","title":null}],"total_grants":6,"fwci":8.4248,"citation_percentile":0.98922676,"influential_citations":6,"citation_trend":[{"year":2016,"count":17},{"year":2017,"count":18},{"year":2018,"count":14},{"year":2019,"count":13},{"year":2020,"count":18},{"year":2021,"count":17},{"year":2022,"count":20},{"year":2023,"count":14},{"year":2024,"count":16},{"year":2025,"count":13},{"year":2026,"count":10}],"oa_status":"bronze","license":"http://www.pnas.org/preview_site/misc/userlicense.xhtml","oa_locations":[{"url":"https://www.pnas.org/content/pnas/113/2/E137.full.pdf","host_type":"journal"},{"url":"https://europepmc.org/articles/pmc4720335?pdf=render","host_type":"GREEN"},{"url":"https://www.pnas.org/content/pnas/113/2/E137.full.pdf","host_type":"publisher"},{"url":"http://www.pnas.org/syndication/doi/10.1073/pnas.1517288113","host_type":"publisher"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.1517288113","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.1517288113","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/26719417","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4720335","host_type":"repository"}],"fields_of_study":["Ion Channels and Receptors","Herbal Medicine Research Studies","Phytochemicals and Antioxidant Activities","Chemistry","Medicine","Amino Acids","Binding Sites","Capsaicin","Cryoelectron Microscopy","Diterpenes","Electricity","Ion Channel Gating","Ligands","Molecular Docking Simulation","Mutagenesis","Mutant Proteins","Static Electricity","TRPV Cation Channels","Water"],"mesh_terms":["Amino Acids","Binding Sites","Capsaicin","Diterpenes","Electricity","Ligands","Water","Ion Channel Gating","Mutagenesis","Cryoelectron Microscopy","Mutant Proteins","TRPV Cation Channels","Static Electricity","Molecular Docking Simulation"],"keywords":["Resiniferatoxin","TRPV1","Capsaicin","Chemistry","Ligand (biochemistry)","Biophysics","Transient receptor potential channel","Receptor","Mutagenesis","Binding site","Cell biology","Biochemistry","Biology","Mutation","docking","heat-sensitive","ligand-gated","nociception","vanilloid"],"sdg_mappings":[],"linked_datasets":[{"doi":"10.6084/m9.figshare.26657224.v1","title":"Additional file 1 of Capsaicin orchestrates metastasis in gastric cancer via modulating expression of TRPV1 channels and driving gut microbiota disorder","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.26657224","title":"Additional file 1 of Capsaicin orchestrates metastasis in gastric cancer via modulating expression of TRPV1 channels and driving gut microbiota disorder","publisher":"figshare","resource_type":"JournalArticle"}],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-08T21:43:19.323660Z","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,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}