{"doi":"10.1039/d1cc03202j","title":"Fragment-based design of selective GPCR ligands guided by free energy simulations","abstract":"Fragment-based drug discovery relies on successful optimization of weakly binding ligands for affinity and selectivity. Herein, we explored strategies for structure-based evolution of fragments binding to a G protein-coupled receptor. Molecular dynamics simulations combined with rigorous free energy calculations guided synthesis of nanomolar ligands with up to >1000-fold improvements of binding affinity and close to 40-fold subtype selectivity.","journal":"Chemical Communications","year":2021,"id":177835,"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":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9448,"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":722806,"name":"Duc Duy Vo","orcid":null,"position":1,"is_corresponding":false},{"id":275808,"name":"Zhan‐Guo Gao","orcid":"0000-0002-6663-524X","position":2,"is_corresponding":false},{"id":722361,"name":"Jan Kihlberg","orcid":"0000-0002-4205-6040","position":3,"is_corresponding":false},{"id":233845,"name":"Kenneth A. Jacobson","orcid":"0000-0001-8104-1493","position":4,"is_corresponding":false},{"id":275811,"name":"Jens Carlsson","orcid":"0000-0003-4623-2977","position":5,"is_corresponding":false},{"id":275809,"name":"Pierre Matricon","orcid":"0000-0001-9350-896X","position":0,"is_corresponding":true}],"reference_count":15,"raw_metadata":null,"created_at":"2026-07-18T23:47:32.096934Z","pmid":"34734588","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":[]}