{"doi":"10.1073/pnas.2101932118","title":"Key computational findings reveal proton transfer as driving the functional cycle in the phosphate transporter PiPT","abstract":"Significance Proton- or sodium-coupled transporters within the major facilitator superfamily are essential for nutrient uptake in all forms of life. We focus on a high-affinity eukaryotic proton-coupled phosphate symporter using extensive classical molecular dynamics (MD) simulations and quantum mechanics/molecular mechanics MD combined with free energy sampling and confirm the role of a key residue, D324, at the molecular level. The results explain the exit direction of the proton once dissociated from D324 and reveal a perspective on proton-coupled transporters, showing that titratable substrates can be involved in the proton transport process as a key aspect of the functional cycle. Mutagenesis and phosphate transport confirm the essential nature of the key D45 residue in the protonation pathway.","journal":"Proceedings of the National Academy of Sciences","year":2021,"id":174483,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":23,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9529,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":363300,"name":"Chenghan Li","orcid":"0000-0001-6095-9318","position":1,"is_corresponding":false},{"id":108109,"name":"Meghna Gupta","orcid":"0000-0002-7432-3211","position":2,"is_corresponding":false},{"id":713999,"name":"Nidhi Verma","orcid":"0000-0003-0643-8858","position":3,"is_corresponding":false},{"id":714000,"name":"Atul Kumar Johri","orcid":"0000-0001-9480-3063","position":4,"is_corresponding":false},{"id":103698,"name":"Robert M. Stroud","orcid":"0000-0003-2083-5665","position":5,"is_corresponding":false},{"id":246697,"name":"Gregory A. Voth","orcid":"0000-0002-3267-6748","position":6,"is_corresponding":false},{"id":598541,"name":"Yu Liu","orcid":"0009-0009-6925-5304","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":null,"created_at":"2026-07-18T23:47:06.584146Z","pmid":"34135124","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":[]}