{"doi":"10.1101/708289","title":"Conformational Transition Pathways in Major Facilitator Superfamily Transporters","abstract":"<jats:p>The major facilitator superfamily (MFS) of transporters contains three classes of membrane transporters: symporters, uniporters, and antiporters. Despite utilizing a variety of transport methods, MFS transporters are believed to undergo similar conformational changes within their distinct transport cycles. Although the similarities regarding conformational changes between the classes of MFS transporters are noteworthy, the differences are also valuable because they may explain the distinct functions of the classes within the MFS. Here, we have performed a variety of equilibrium and non-equilibrium all-atom molecular dynamics (MD) simulations of the bacterial proton-coupled oligopeptide transporter (GkPOT) and the human glucose transporter 1 (GluT1). To compare the similarities and differences of the conformational dynamics found within the three different classes of transporters we have also referenced previous simulations involving the glycerol-3-phosphate (GlpT) transporter. All of the proteins discussed here were simulated in the {\\it apo} state in explicit membrane environments. Our results suggest a very similar conformational transition for all transporter types involving interbundle salt-bridge formation/disruption coupled with the orientation changes of transmembrane (TM) helices, specifically H1/H7 and H5/H11, resulting in an alternation in the accessibility of water at the cyto- and periplasmic gates.</jats:p>","journal":null,"year":null,"id":591860,"datarank":0.2516625461546648,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.010246859289549768,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.010246859289549768,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":1,"citers_with_citation_signal":1,"citers_with_endowment":1,"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":336065,"name":"Kalyan Immadisetty","orcid":"0000-0001-8261-6770","position":1,"is_corresponding":false},{"id":1044636,"name":"Stephanie Sauve","orcid":null,"position":2,"is_corresponding":false},{"id":564984,"name":"Mahmoud Moradi","orcid":"0000-0002-0601-402X","position":3,"is_corresponding":false},{"id":1514402,"name":"Dylan Ogden","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Conformational Transition Pathways in Major Facilitator Superfamily Transporters","abstract":"<jats:p>The major facilitator superfamily (MFS) of transporters contains three classes of membrane transporters: symporters, uniporters, and antiporters. Despite utilizing a variety of transport methods, MFS transporters are believed to undergo similar conformational changes within their distinct transport cycles. Although the similarities regarding conformational changes between the classes of MFS transporters are noteworthy, the differences are also valuable because they may explain the distinct functions of the classes within the MFS. Here, we have performed a variety of equilibrium and non-equilibrium all-atom molecular dynamics (MD) simulations of the bacterial proton-coupled oligopeptide transporter (GkPOT) and the human glucose transporter 1 (GluT1). To compare the similarities and differences of the conformational dynamics found within the three different classes of transporters we have also referenced previous simulations involving the glycerol-3-phosphate (GlpT) transporter. All of the proteins discussed here were simulated in the {\\it apo} state in explicit membrane environments. Our results suggest a very similar conformational transition for all transporter types involving interbundle salt-bridge formation/disruption coupled with the orientation changes of transmembrane (TM) helices, specifically H1/H7 and H5/H11, resulting in an alternation in the accessibility of water at the cyto- and periplasmic gates.</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":null,"pmcid":null,"openalex_id":null,"authors":[],"funders":[{"funder_name":"National Science Foundation","grant_id":"1238993","title":"Sustained-Petascale In Action: Blue Waters Enabling Transformative Science And Engineering"},{"funder_name":"National Science Foundation","grant_id":"0725070","title":"Leadership Class Scientific and Engineering Computing: Breaking Through the Limits"}],"total_grants":2,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":null,"license":"https://www.biorxiv.org/about/FAQ#license","oa_locations":[{"url":"https://syndication.highwire.org/content/doi/10.1101/708289","host_type":"publisher"},{"url":"https://doi.org/10.1101/708289","host_type":""},{"url":"https://www.biorxiv.org/content/biorxiv/early/2019/09/04/708289.full.pdf","host_type":""},{"url":"https://dx.doi.org/10.1101/708289","host_type":""},{"url":"http://dx.doi.org/10.1101/708289","host_type":""}],"fields_of_study":["0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":[],"keywords":[],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-26T11:02:19.903335Z","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":[]}