{"id":"https://openalex.org/W4365458525","doi":"https://doi.org/10.1021/acs.jcim.3c00042","title":"Unbinding Kinetics of Muscarinic M3 Receptor Antagonists Explained by Metadynamics Simulations","display_name":"Unbinding Kinetics of Muscarinic M3 Receptor Antagonists Explained by Metadynamics Simulations","publication_year":2023,"publication_date":"2023-04-13","ids":{"openalex":"https://openalex.org/W4365458525","doi":"https://doi.org/10.1021/acs.jcim.3c00042","pmid":"https://pubmed.ncbi.nlm.nih.gov/37053454"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.3c00042","is_oa":true,"landing_page_url":"https://doi.org/10.1021/acs.jcim.3c00042","pdf_url":null,"source":{"id":"https://openalex.org/S167262187","display_name":"Journal of Chemical Information and Modeling","issn_l":"1549-9596","issn":["1549-9596","1549-960X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Chemical Information and Modeling","raw_type":"journal-article"},"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"hybrid","oa_url":"https://doi.org/10.1021/acs.jcim.3c00042","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5056263033","display_name":"Francesca Galvani","orcid":"https://orcid.org/0000-0002-7543-9945"},"institutions":[{"id":"https://openalex.org/I124601658","display_name":"University of Parma","ror":"https://ror.org/02k7wn190","country_code":"IT","type":"education","lineage":["https://openalex.org/I124601658"]}],"countries":["IT"],"is_corresponding":false,"raw_author_name":"Francesca Galvani","raw_affiliation_strings":["Dipartimento di Scienze degli Alimenti e del Farmaco, Universit\u00e0 degli Studi di Parma, Parco Area delle Scienze 27/A, I-43124 Parma, Italy"],"affiliations":[{"raw_affiliation_string":"Dipartimento di Scienze degli Alimenti e del Farmaco, Universit\u00e0 degli Studi di Parma, Parco Area delle Scienze 27/A, I-43124 Parma, Italy","institution_ids":["https://openalex.org/I124601658"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5067645091","display_name":"Daniele Pala","orcid":"https://orcid.org/0000-0001-6160-6127"},"institutions":[{"id":"https://openalex.org/I4210162628","display_name":"Chiesi (Italy)","ror":"https://ror.org/0511bn634","country_code":"IT","type":"company","lineage":["https://openalex.org/I4210162628"]}],"countries":["IT"],"is_corresponding":false,"raw_author_name":"Daniele Pala","raw_affiliation_strings":["Chemistry Research and Drug Design Department, Chiesi Farmaceutici S.p.A., Largo F. Belloli 11/A, 43122 Parma, Italy"],"affiliations":[{"raw_affiliation_string":"Chemistry Research and Drug Design Department, Chiesi Farmaceutici S.p.A., Largo F. Belloli 11/A, 43122 Parma, Italy","institution_ids":["https://openalex.org/I4210162628"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5049972475","display_name":"Alberto Cuzzolin","orcid":null},"institutions":[{"id":"https://openalex.org/I4210162628","display_name":"Chiesi (Italy)","ror":"https://ror.org/0511bn634","country_code":"IT","type":"company","lineage":["https://openalex.org/I4210162628"]}],"countries":["IT"],"is_corresponding":false,"raw_author_name":"Alberto Cuzzolin","raw_affiliation_strings":["Chemistry Research and Drug Design Department, Chiesi Farmaceutici S.p.A., Largo F. Belloli 11/A, 43122 Parma, Italy"],"affiliations":[{"raw_affiliation_string":"Chemistry Research and Drug Design Department, Chiesi Farmaceutici S.p.A., Largo F. Belloli 11/A, 43122 Parma, Italy","institution_ids":["https://openalex.org/I4210162628"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5043710547","display_name":"Laura Scalvini","orcid":"https://orcid.org/0000-0003-3610-527X"},"institutions":[{"id":"https://openalex.org/I124601658","display_name":"University of Parma","ror":"https://ror.org/02k7wn190","country_code":"IT","type":"education","lineage":["https://openalex.org/I124601658"]}],"countries":["IT"],"is_corresponding":false,"raw_author_name":"Laura Scalvini","raw_affiliation_strings":["Dipartimento di Scienze degli Alimenti e del Farmaco, Universit\u00e0 degli Studi di Parma, Parco Area delle Scienze 27/A, I-43124 Parma, Italy"],"affiliations":[{"raw_affiliation_string":"Dipartimento di Scienze degli Alimenti e del Farmaco, Universit\u00e0 degli Studi di Parma, Parco Area delle Scienze 27/A, I-43124 Parma, Italy","institution_ids":["https://openalex.org/I124601658"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5042341429","display_name":"Alessio Lodola","orcid":"https://orcid.org/0000-0002-8675-1002"},"institutions":[{"id":"https://openalex.org/I124601658","display_name":"University of Parma","ror":"https://ror.org/02k7wn190","country_code":"IT","type":"education","lineage":["https://openalex.org/I124601658"]}],"countries":["IT"],"is_corresponding":true,"raw_author_name":"Alessio Lodola","raw_affiliation_strings":["Dipartimento di Scienze degli Alimenti e del Farmaco, Universit\u00e0 degli Studi di Parma, Parco Area delle Scienze 27/A, I-43124 Parma, Italy"],"affiliations":[{"raw_affiliation_string":"Dipartimento di Scienze degli Alimenti e del Farmaco, Universit\u00e0 degli Studi di Parma, Parco Area delle Scienze 27/A, I-43124 Parma, Italy","institution_ids":["https://openalex.org/I124601658"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5085013575","display_name":"Marco Mor","orcid":"https://orcid.org/0000-0003-0199-1849"},"institutions":[{"id":"https://openalex.org/I124601658","display_name":"University of Parma","ror":"https://ror.org/02k7wn190","country_code":"IT","type":"education","lineage":["https://openalex.org/I124601658"]}],"countries":["IT"],"is_corresponding":false,"raw_author_name":"Marco Mor","raw_affiliation_strings":["Dipartimento di Scienze degli Alimenti e del Farmaco, Universit\u00e0 degli Studi di Parma, Parco Area delle Scienze 27/A, I-43124 Parma, Italy","Microbiome Research Hub, University of Parma, Parco Area delle Scienze 11/A, I-43124 Parma, Italy"],"affiliations":[{"raw_affiliation_string":"Dipartimento di Scienze degli Alimenti e del Farmaco, Universit\u00e0 degli Studi di Parma, Parco Area delle Scienze 27/A, I-43124 Parma, Italy","institution_ids":["https://openalex.org/I124601658"]},{"raw_affiliation_string":"Microbiome Research Hub, University of Parma, Parco Area delle Scienze 11/A, I-43124 Parma, Italy","institution_ids":["https://openalex.org/I124601658"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5026440664","display_name":"Andrea Rizzi","orcid":"https://orcid.org/0000-0001-7693-2013"},"institutions":[{"id":"https://openalex.org/I4210162628","display_name":"Chiesi (Italy)","ror":"https://ror.org/0511bn634","country_code":"IT","type":"company","lineage":["https://openalex.org/I4210162628"]}],"countries":["IT"],"is_corresponding":false,"raw_author_name":"Andrea Rizzi","raw_affiliation_strings":["Chemistry Research and Drug Design Department, Chiesi Farmaceutici S.p.A., Largo F. Belloli 11/A, 43122 Parma, Italy"],"affiliations":[{"raw_affiliation_string":"Chemistry Research and Drug Design Department, Chiesi Farmaceutici S.p.A., Largo F. Belloli 11/A, 43122 Parma, Italy","institution_ids":["https://openalex.org/I4210162628"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":7,"corresponding_author_ids":["https://openalex.org/A5042341429"],"corresponding_institution_ids":["https://openalex.org/I124601658"],"apc_list":null,"apc_paid":null,"fwci":2.0011,"has_fulltext":true,"cited_by_count":13,"citation_normalized_percentile":{"value":0.86239979,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":90,"max":99},"biblio":{"volume":"63","issue":"9","first_page":"2842","last_page":"2856"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11178","display_name":"Receptor Mechanisms and Signaling","score":0.9998000264167786,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T11178","display_name":"Receptor Mechanisms and Signaling","score":0.9998000264167786,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11016","display_name":"Monoclonal and Polyclonal Antibodies Research","score":0.9872000217437744,"subfield":{"id":"https://openalex.org/subfields/2741","display_name":"Radiology, Nuclear Medicine and Imaging"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10044","display_name":"Protein Structure and Dynamics","score":0.9793000221252441,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/metadynamics","display_name":"Metadynamics","score":0.696618378162384},{"id":"https://openalex.org/keywords/kinetics","display_name":"Kinetics","score":0.6418969035148621},{"id":"https://openalex.org/keywords/biological-system","display_name":"Biological system","score":0.5677524209022522},{"id":"https://openalex.org/keywords/chemistry","display_name":"Chemistry","score":0.5346072912216187},{"id":"https://openalex.org/keywords/molecular-dynamics","display_name":"Molecular dynamics","score":0.46980342268943787},{"id":"https://openalex.org/keywords/acceleration","display_name":"Acceleration","score":0.4468819797039032},{"id":"https://openalex.org/keywords/statistical-physics","display_name":"Statistical physics","score":0.3976217806339264},{"id":"https://openalex.org/keywords/computational-chemistry","display_name":"Computational chemistry","score":0.37158727645874023},{"id":"https://openalex.org/keywords/thermodynamics","display_name":"Thermodynamics","score":0.3627416789531708},{"id":"https://openalex.org/keywords/computer-science","display_name":"Computer science","score":0.33793115615844727},{"id":"https://openalex.org/keywords/physics","display_name":"Physics","score":0.26683446764945984},{"id":"https://openalex.org/keywords/biology","display_name":"Biology","score":0.096048504114151}],"concepts":[{"id":"https://openalex.org/C62752575","wikidata":"https://www.wikidata.org/wiki/Q6822487","display_name":"Metadynamics","level":3,"score":0.696618378162384},{"id":"https://openalex.org/C148898269","wikidata":"https://www.wikidata.org/wiki/Q1108792","display_name":"Kinetics","level":2,"score":0.6418969035148621},{"id":"https://openalex.org/C186060115","wikidata":"https://www.wikidata.org/wiki/Q30336093","display_name":"Biological system","level":1,"score":0.5677524209022522},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.5346072912216187},{"id":"https://openalex.org/C59593255","wikidata":"https://www.wikidata.org/wiki/Q901663","display_name":"Molecular dynamics","level":2,"score":0.46980342268943787},{"id":"https://openalex.org/C117896860","wikidata":"https://www.wikidata.org/wiki/Q11376","display_name":"Acceleration","level":2,"score":0.4468819797039032},{"id":"https://openalex.org/C121864883","wikidata":"https://www.wikidata.org/wiki/Q677916","display_name":"Statistical physics","level":1,"score":0.3976217806339264},{"id":"https://openalex.org/C147597530","wikidata":"https://www.wikidata.org/wiki/Q369472","display_name":"Computational chemistry","level":1,"score":0.37158727645874023},{"id":"https://openalex.org/C97355855","wikidata":"https://www.wikidata.org/wiki/Q11473","display_name":"Thermodynamics","level":1,"score":0.3627416789531708},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.33793115615844727},{"id":"https://openalex.org/C121332964","wikidata":"https://www.wikidata.org/wiki/Q413","display_name":"Physics","level":0,"score":0.26683446764945984},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.096048504114151},{"id":"https://openalex.org/C62520636","wikidata":"https://www.wikidata.org/wiki/Q944","display_name":"Quantum mechanics","level":1,"score":0.0},{"id":"https://openalex.org/C74650414","wikidata":"https://www.wikidata.org/wiki/Q11397","display_name":"Classical mechanics","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D007700","descriptor_name":"Kinetics","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D007700","descriptor_name":"Kinetics","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D007700","descriptor_name":"Kinetics","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D007700","descriptor_name":"Kinetics","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008024","descriptor_name":"Ligands","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008024","descriptor_name":"Ligands","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008024","descriptor_name":"Ligands","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008024","descriptor_name":"Ligands","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D010825","descriptor_name":"Physics","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D010825","descriptor_name":"Physics","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D010825","descriptor_name":"Physics","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D010825","descriptor_name":"Physics","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D043587","descriptor_name":"Receptor, Muscarinic M3","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D043587","descriptor_name":"Receptor, Muscarinic M3","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D043587","descriptor_name":"Receptor, Muscarinic M3","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D043587","descriptor_name":"Receptor, Muscarinic M3","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D056004","descriptor_name":"Molecular Dynamics Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D056004","descriptor_name":"Molecular Dynamics Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D056004","descriptor_name":"Molecular Dynamics Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D056004","descriptor_name":"Molecular Dynamics Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true}],"locations_count":3,"locations":[{"id":"doi:10.1021/acs.jcim.3c00042","is_oa":true,"landing_page_url":"https://doi.org/10.1021/acs.jcim.3c00042","pdf_url":null,"source":{"id":"https://openalex.org/S167262187","display_name":"Journal of Chemical Information and Modeling","issn_l":"1549-9596","issn":["1549-9596","1549-960X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Chemical Information and Modeling","raw_type":"journal-article"},{"id":"pmid:37053454","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/37053454","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of chemical information and modeling","raw_type":null},{"id":"pmh:oai:pubmedcentral.nih.gov:10170513","is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10170513","pdf_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10170513/pdf/ci3c00042.pdf","source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"J Chem Inf Model","raw_type":"Text"}],"best_oa_location":{"id":"doi:10.1021/acs.jcim.3c00042","is_oa":true,"landing_page_url":"https://doi.org/10.1021/acs.jcim.3c00042","pdf_url":null,"source":{"id":"https://openalex.org/S167262187","display_name":"Journal of Chemical Information and Modeling","issn_l":"1549-9596","issn":["1549-9596","1549-960X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Chemical Information and Modeling","raw_type":"journal-article"},"sustainable_development_goals":[{"score":0.49000000953674316,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"awards":[],"funders":[{"id":"https://openalex.org/F4320326075","display_name":"Regione Emilia-Romagna","ror":null}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":69,"referenced_works":["https://openalex.org/W1230652463","https://openalex.org/W1968620174","https://openalex.org/W1974880836","https://openalex.org/W1975732928","https://openalex.org/W1977459493","https://openalex.org/W1985588649","https://openalex.org/W1987048011","https://openalex.org/W1992899488","https://openalex.org/W1994941561","https://openalex.org/W1998404217","https://openalex.org/W1999522888","https://openalex.org/W2001357862","https://openalex.org/W2017128003","https://openalex.org/W2019263601","https://openalex.org/W2030835797","https://openalex.org/W2035527380","https://openalex.org/W2040680919","https://openalex.org/W2040757185","https://openalex.org/W2047144511","https://openalex.org/W2056765555","https://openalex.org/W2057806291","https://openalex.org/W2061312993","https://openalex.org/W2063945425","https://openalex.org/W2067174909","https://openalex.org/W2073263185","https://openalex.org/W2085829368","https://openalex.org/W2086729168","https://openalex.org/W2105398220","https://openalex.org/W2130212172","https://openalex.org/W2145005201","https://openalex.org/W2149141089","https://openalex.org/W2207535250","https://openalex.org/W2271736303","https://openalex.org/W2287402248","https://openalex.org/W2316118030","https://openalex.org/W2325632106","https://openalex.org/W2346925722","https://openalex.org/W2404651707","https://openalex.org/W2414725821","https://openalex.org/W2529600645","https://openalex.org/W2567204400","https://openalex.org/W2575009204","https://openalex.org/W2598374175","https://openalex.org/W2625293850","https://openalex.org/W2741577472","https://openalex.org/W2804603144","https://openalex.org/W2883643505","https://openalex.org/W2900014623","https://openalex.org/W2918125819","https://openalex.org/W2924677843","https://openalex.org/W2944207598","https://openalex.org/W2953107349","https://openalex.org/W2956011600","https://openalex.org/W3010353326","https://openalex.org/W3016343496","https://openalex.org/W3036901602","https://openalex.org/W3043528025","https://openalex.org/W3090513030","https://openalex.org/W3167019654","https://openalex.org/W3172790545","https://openalex.org/W3198320390","https://openalex.org/W4200490539","https://openalex.org/W4233334497","https://openalex.org/W4255486780","https://openalex.org/W4285744851","https://openalex.org/W4288429767","https://openalex.org/W4313453532","https://openalex.org/W4319815296","https://openalex.org/W4384615983"],"related_works":["https://openalex.org/W2599759970","https://openalex.org/W1633592986","https://openalex.org/W1979607105","https://openalex.org/W2020879467","https://openalex.org/W4385857439","https://openalex.org/W1970701509","https://openalex.org/W2111128714","https://openalex.org/W4220878319","https://openalex.org/W3083266070","https://openalex.org/W4242006566"],"abstract_inverted_index":{"The":[0,23],"residence":[1],"time":[2,5,97,141],"(RT),":[3],"the":[4,40,46,59,67,72,76,88,93,99,103,113,123,128,135,140,147,150,154,164,172,205,212],"for":[6,20,117,169],"which":[7],"a":[8,17,83,118,131,208,216],"drug":[9,21],"remains":[10],"bound":[11,104],"to":[12,33,57,111,145,153,162,184,203],"its":[13],"biological":[14],"target,":[15],"is":[16,80,109,137],"critical":[18],"parameter":[19,85],"design.":[22],"prediction":[24],"of":[25,42,61,78,98,120,134,142,166,207],"this":[26],"key":[27],"kinetic":[28],"property":[29],"has":[30,159,219],"been":[31,160,220],"proven":[32],"be":[34,199],"challenging":[35],"and":[36,51,201],"computationally":[37],"demanding":[38],"in":[39,102,187],"framework":[41],"atomistic":[43],"simulations.":[44],"In":[45,66,122],"present":[47],"work,":[48],"we":[49],"setup":[50],"applied":[52],"two":[53],"distinct":[54],"metadynamics":[55],"protocols":[56,181],"estimate":[58],"RTs":[60,168],"muscarinic":[62],"M3":[63],"receptor":[64],"antagonists.":[65],"first":[68],"method,":[69,125],"derived":[70],"from":[71,82,149],"conformational":[73],"flooding":[74],"approach,":[75,130],"kinetics":[77],"unbinding":[79],"retrieved":[81],"physics-based":[84],"known":[86,126],"as":[87,127],"acceleration":[89],"factor":[90],"\u03b1":[91],"(i.e.,":[92],"running":[94],"average":[95],"over":[96],"potential":[100],"deposited":[101],"state).":[105],"Such":[106],"an":[107],"approach":[108,158],"expected":[110],"recover":[112],"absolute":[114],"RT":[115,136,214],"value":[116],"compound":[119],"interest.":[121],"second":[124],"<i>t</i><sub>META-D</sub>":[129],"qualitative":[132],"estimation":[133],"given":[138],"by":[139],"simulation":[143],"required":[144],"drive":[146],"ligand":[148],"binding":[151],"site":[152],"solvent":[155],"bulk.":[156],"This":[157],"developed":[161],"reproduce":[163],"change":[165],"experimental":[167,191,213],"compounds":[170,186],"targeting":[171],"same":[173],"target.":[174],"Our":[175],"analysis":[176],"shows":[177],"that":[178],"both":[179],"computational":[180],"are":[182],"able":[183],"rank":[185],"agreement":[188],"with":[189],"their":[190],"RTs.":[192],"Quantitative":[193],"structure-kinetics":[194],"relationship":[195],"(SKR)":[196],"models":[197],"can":[198],"identified":[200],"employed":[202],"predict":[204],"impact":[206],"chemical":[209],"modification":[210],"on":[211],"once":[215],"calibration":[217],"study":[218],"performed.":[221]},"counts_by_year":[{"year":2026,"cited_by_count":1},{"year":2025,"cited_by_count":8},{"year":2024,"cited_by_count":1},{"year":2023,"cited_by_count":3}],"updated_date":"2026-03-27T05:58:40.876381","created_date":"2025-10-10T00:00:00"}