{"doi":"10.1039/c6mb00630b","title":"Allosteric pathways in tetrahydrofolate sensing riboswitch with dynamics correlation network","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Riboswitches are cis-acting genetic control elements. Due to their fundamental importance in bacteria gene regulation, they have been proposed as antibacterial drug targets. Tetrahydrofolate (THF) is an essential cofactor of one-carbon transfer reactions and downregulates the expression of downstream genes. However, information on how to transfer from the binding site of THF to the expression platform is still unavailable. Herein, a nucleotide/nucleotide dynamics correlation network based on an all-atom molecular dynamic simulation was used to reveal the regulation mechanism of a THF-sensing riboswitch. Shortest pathway analysis based on the network illustrates that there is an allosteric pathway through the P2 helix to the pseudoknot, then to the P1 helix in the THF-riboswitch. Thus the hypothesis of “THF-binding induced allosteric switching” was proposed and evaluated using THF and pseudoknot weakened experiments. Furthermore, a possible allosteric pathway of C30–C31–G33–A34–G35–G36–G37–A38–G48–G47–U46–A90–U91–C92–G93–C94–G95–C96 was identified and confirmed through the perturbation of the network. The proposed allosteric mechanism and the underlying allosteric pathway provide fundamental insights for the regulation of THF sensing riboswitches.</jats:p>\n                  <jats:p/>","journal":"Molecular BioSystems","year":2016,"id":673352,"datarank":0.32958368660043297,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.0,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"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":1160383,"name":"Cheng Jiang","orcid":"0009-0003-2170-2538","position":1,"is_corresponding":false},{"id":681929,"name":"Wei Ye","orcid":"0000-0002-3980-8547","position":2,"is_corresponding":false},{"id":39810,"name":"Ray Luo","orcid":"0000-0002-6346-8271","position":3,"is_corresponding":false},{"id":1508188,"name":"Hai-Feng Chen","orcid":null,"position":4,"is_corresponding":false},{"id":1759268,"name":"Jin-Mai Zhang","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Allosteric pathways in tetrahydrofolate sensing riboswitch with dynamics correlation network","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Riboswitches are cis-acting genetic control elements. Due to their fundamental importance in bacteria gene regulation, they have been proposed as antibacterial drug targets. Tetrahydrofolate (THF) is an essential cofactor of one-carbon transfer reactions and downregulates the expression of downstream genes. However, information on how to transfer from the binding site of THF to the expression platform is still unavailable. Herein, a nucleotide/nucleotide dynamics correlation network based on an all-atom molecular dynamic simulation was used to reveal the regulation mechanism of a THF-sensing riboswitch. Shortest pathway analysis based on the network illustrates that there is an allosteric pathway through the P2 helix to the pseudoknot, then to the P1 helix in the THF-riboswitch. Thus the hypothesis of “THF-binding induced allosteric switching” was proposed and evaluated using THF and pseudoknot weakened experiments. Furthermore, a possible allosteric pathway of C30–C31–G33–A34–G35–G36–G37–A38–G48–G47–U46–A90–U91–C92–G93–C94–G95–C96 was identified and confirmed through the perturbation of the network. The proposed allosteric mechanism and the underlying allosteric pathway provide fundamental insights for the regulation of THF sensing riboswitches.</jats:p>\n                  <jats:p/>","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":"27841427","pmcid":"PMC5173395","openalex_id":"https://openalex.org/W2543514139","authors":[],"funders":[{"funder_name":"NIAAA NIH HHS","grant_id":"R34 AA021502","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM079383","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM093040","title":null}],"total_grants":3,"fwci":0.8009,"citation_percentile":0.75224589,"influential_citations":0,"citation_trend":[{"year":2018,"count":3},{"year":2019,"count":2},{"year":2021,"count":1},{"year":2024,"count":1},{"year":2025,"count":1}],"oa_status":"green","license":"https://academic.oup.com/pages/standard-publication-reuse-rights","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5173395","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5173395","host_type":"repository"},{"url":"https://academic.oup.com/molecular-omics/article-pdf/13/1/156/65480641/c6mb00630b.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1039/c6mb00630b","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/27841427","host_type":"repository"},{"url":"https://escholarship.org/uc/item/3q08p3jr","host_type":"repository"}],"fields_of_study":["RNA and protein synthesis mechanisms","RNA modifications and cancer","RNA Research and Splicing"],"mesh_terms":["Allosteric Regulation","Molecular Conformation","Magnetic Resonance Spectroscopy","Nucleic Acid Conformation","RNA, Messenger","Tetrahydrofolates","Molecular Dynamics Simulation","Riboswitch"],"keywords":["Allosteric regulation","Riboswitch","Chemistry","Allosteric enzyme","Computational biology","Biophysics","Biology","Biochemistry","Enzyme","Gene expression","Gene"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Clean water and sanitation"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"pdb"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-16T13:10:51.866508Z","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":[]}