{"id":"https://openalex.org/W7117150337","doi":"https://doi.org/10.1021/acs.jcim.5c02583","title":"Structural and Computational Insights into the Mechanism of the Superior Pharmacological Activity of Crisugabalin: A Third-Generation Cav\u03b1 <sub>2</sub> \u03b41 Ligand","display_name":"Structural and Computational Insights into the Mechanism of the Superior Pharmacological Activity of Crisugabalin: A Third-Generation Cav\u03b1 <sub>2</sub> \u03b41 Ligand","publication_year":2025,"publication_date":"2025-12-24","ids":{"openalex":"https://openalex.org/W7117150337","doi":"https://doi.org/10.1021/acs.jcim.5c02583","pmid":"https://pubmed.ncbi.nlm.nih.gov/41439594"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.5c02583","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.5c02583","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":null,"license_id":null,"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":"green","oa_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12802839/","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5121225241","display_name":"Zhaoqiang Chen","orcid":null},"institutions":[{"id":"https://openalex.org/I4210135994","display_name":"China Railway Group (China)","ror":"https://ror.org/03za3eq42","country_code":"CN","type":"company","lineage":["https://openalex.org/I4210135994"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Zhaoqiang Chen","raw_affiliation_strings":["Haisco Pharmaceutical Group Co, Ltd, 136 Baili Rd, Wenjiang District, Chengdu, Sichuan 611130, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Haisco Pharmaceutical Group Co, Ltd, 136 Baili Rd, Wenjiang District, Chengdu, Sichuan 611130, China","institution_ids":["https://openalex.org/I4210135994"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5112567231","display_name":"Xiaoli Gou","orcid":null},"institutions":[{"id":"https://openalex.org/I4210135994","display_name":"China Railway Group (China)","ror":"https://ror.org/03za3eq42","country_code":"CN","type":"company","lineage":["https://openalex.org/I4210135994"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Xiaoli Gou","raw_affiliation_strings":["Haisco Pharmaceutical Group Co, Ltd, 136 Baili Rd, Wenjiang District, Chengdu, Sichuan 611130, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Haisco Pharmaceutical Group Co, Ltd, 136 Baili Rd, Wenjiang District, Chengdu, Sichuan 611130, China","institution_ids":["https://openalex.org/I4210135994"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5121214318","display_name":"Qingyuan Meng","orcid":null},"institutions":[{"id":"https://openalex.org/I4210135994","display_name":"China Railway Group (China)","ror":"https://ror.org/03za3eq42","country_code":"CN","type":"company","lineage":["https://openalex.org/I4210135994"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Qingyuan Meng","raw_affiliation_strings":["Haisco Pharmaceutical Group Co, Ltd, 136 Baili Rd, Wenjiang District, Chengdu, Sichuan 611130, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Haisco Pharmaceutical Group Co, Ltd, 136 Baili Rd, Wenjiang District, Chengdu, Sichuan 611130, China","institution_ids":["https://openalex.org/I4210135994"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5121189501","display_name":"He Li","orcid":null},"institutions":[{"id":"https://openalex.org/I4210135994","display_name":"China Railway Group (China)","ror":"https://ror.org/03za3eq42","country_code":"CN","type":"company","lineage":["https://openalex.org/I4210135994"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"He Li","raw_affiliation_strings":["Haisco Pharmaceutical Group Co, Ltd, 136 Baili Rd, Wenjiang District, Chengdu, Sichuan 611130, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Haisco Pharmaceutical Group Co, Ltd, 136 Baili Rd, Wenjiang District, Chengdu, Sichuan 611130, China","institution_ids":["https://openalex.org/I4210135994"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5121152794","display_name":"Yao Li","orcid":null},"institutions":[{"id":"https://openalex.org/I4210135994","display_name":"China Railway Group (China)","ror":"https://ror.org/03za3eq42","country_code":"CN","type":"company","lineage":["https://openalex.org/I4210135994"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Yao Li","raw_affiliation_strings":["Haisco Pharmaceutical Group Co, Ltd, 136 Baili Rd, Wenjiang District, Chengdu, Sichuan 611130, China"],"raw_orcid":"https://orcid.org/0000-0001-5760-9421","affiliations":[{"raw_affiliation_string":"Haisco Pharmaceutical Group Co, Ltd, 136 Baili Rd, Wenjiang District, Chengdu, Sichuan 611130, China","institution_ids":["https://openalex.org/I4210135994"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5110489017","display_name":"Zongjun Shi","orcid":null},"institutions":[{"id":"https://openalex.org/I4210135994","display_name":"China Railway Group (China)","ror":"https://ror.org/03za3eq42","country_code":"CN","type":"company","lineage":["https://openalex.org/I4210135994"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Zongjun Shi","raw_affiliation_strings":["Haisco Pharmaceutical Group Co, Ltd, 136 Baili Rd, Wenjiang District, Chengdu, Sichuan 611130, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Haisco Pharmaceutical Group Co, Ltd, 136 Baili Rd, Wenjiang District, Chengdu, Sichuan 611130, China","institution_ids":["https://openalex.org/I4210135994"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5121179605","display_name":"Xinxin Li","orcid":null},"institutions":[{"id":"https://openalex.org/I4210135994","display_name":"China Railway Group (China)","ror":"https://ror.org/03za3eq42","country_code":"CN","type":"company","lineage":["https://openalex.org/I4210135994"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Xinxin Li","raw_affiliation_strings":["Haisco Pharmaceutical Group Co, Ltd, 136 Baili Rd, Wenjiang District, Chengdu, Sichuan 611130, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Haisco Pharmaceutical Group Co, Ltd, 136 Baili Rd, Wenjiang District, Chengdu, Sichuan 611130, China","institution_ids":["https://openalex.org/I4210135994"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5030392750","display_name":"J. Wang","orcid":null},"institutions":[{"id":"https://openalex.org/I4210135994","display_name":"China Railway Group (China)","ror":"https://ror.org/03za3eq42","country_code":"CN","type":"company","lineage":["https://openalex.org/I4210135994"]}],"countries":["CN"],"is_corresponding":true,"raw_author_name":"Ju Wang","raw_affiliation_strings":["Haisco Pharmaceutical Group Co, Ltd, 136 Baili Rd, Wenjiang District, Chengdu, Sichuan 611130, China"],"raw_orcid":"https://orcid.org/0009-0003-6276-1446","affiliations":[{"raw_affiliation_string":"Haisco Pharmaceutical Group Co, Ltd, 136 Baili Rd, Wenjiang District, Chengdu, Sichuan 611130, China","institution_ids":["https://openalex.org/I4210135994"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5030392750"],"corresponding_institution_ids":["https://openalex.org/I4210135994"],"apc_list":null,"apc_paid":null,"fwci":0.7367,"has_fulltext":false,"cited_by_count":1,"citation_normalized_percentile":{"value":0.78346683,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":94,"max":97},"biblio":{"volume":"66","issue":"1","first_page":"632","last_page":"641"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10196","display_name":"Pain Mechanisms and Treatments","score":0.4059999883174896,"subfield":{"id":"https://openalex.org/subfields/2737","display_name":"Physiology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10196","display_name":"Pain Mechanisms and Treatments","score":0.4059999883174896,"subfield":{"id":"https://openalex.org/subfields/2737","display_name":"Physiology"},"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/T10414","display_name":"Cannabis and Cannabinoid Research","score":0.09019999951124191,"subfield":{"id":"https://openalex.org/subfields/2736","display_name":"Pharmacology"},"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/T11752","display_name":"Cancer Treatment and Pharmacology","score":0.0851999968290329,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/molecular-dynamics","display_name":"Molecular dynamics","score":0.6762999892234802},{"id":"https://openalex.org/keywords/pharmacophore","display_name":"Pharmacophore","score":0.6753000020980835},{"id":"https://openalex.org/keywords/dissociation","display_name":"Dissociation (chemistry)","score":0.6011999845504761},{"id":"https://openalex.org/keywords/tricyclic","display_name":"Tricyclic","score":0.600600004196167},{"id":"https://openalex.org/keywords/pregabalin","display_name":"Pregabalin","score":0.5730000138282776},{"id":"https://openalex.org/keywords/hydrogen-bond","display_name":"Hydrogen bond","score":0.5527999997138977},{"id":"https://openalex.org/keywords/ligand","display_name":"Ligand (biochemistry)","score":0.5181000232696533},{"id":"https://openalex.org/keywords/docking","display_name":"Docking (animal)","score":0.40230000019073486}],"concepts":[{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.859499990940094},{"id":"https://openalex.org/C59593255","wikidata":"https://www.wikidata.org/wiki/Q901663","display_name":"Molecular dynamics","level":2,"score":0.6762999892234802},{"id":"https://openalex.org/C56173144","wikidata":"https://www.wikidata.org/wiki/Q1539893","display_name":"Pharmacophore","level":2,"score":0.6753000020980835},{"id":"https://openalex.org/C102931765","wikidata":"https://www.wikidata.org/wiki/Q189673","display_name":"Dissociation (chemistry)","level":2,"score":0.6011999845504761},{"id":"https://openalex.org/C2781081902","wikidata":"https://www.wikidata.org/wiki/Q3539074","display_name":"Tricyclic","level":2,"score":0.600600004196167},{"id":"https://openalex.org/C2776468701","wikidata":"https://www.wikidata.org/wiki/Q412174","display_name":"Pregabalin","level":2,"score":0.5730000138282776},{"id":"https://openalex.org/C112887158","wikidata":"https://www.wikidata.org/wiki/Q169324","display_name":"Hydrogen bond","level":3,"score":0.5527999997138977},{"id":"https://openalex.org/C116569031","wikidata":"https://www.wikidata.org/wiki/Q899107","display_name":"Ligand (biochemistry)","level":3,"score":0.5181000232696533},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.5037999749183655},{"id":"https://openalex.org/C147597530","wikidata":"https://www.wikidata.org/wiki/Q369472","display_name":"Computational chemistry","level":1,"score":0.429500013589859},{"id":"https://openalex.org/C41685203","wikidata":"https://www.wikidata.org/wiki/Q1974042","display_name":"Docking (animal)","level":2,"score":0.40230000019073486},{"id":"https://openalex.org/C178910836","wikidata":"https://www.wikidata.org/wiki/Q2196961","display_name":"Molecular model","level":2,"score":0.36970001459121704},{"id":"https://openalex.org/C148898269","wikidata":"https://www.wikidata.org/wiki/Q1108792","display_name":"Kinetics","level":2,"score":0.33640000224113464},{"id":"https://openalex.org/C104292427","wikidata":"https://www.wikidata.org/wiki/Q899781","display_name":"Protein subunit","level":3,"score":0.3287000060081482},{"id":"https://openalex.org/C90260826","wikidata":"https://www.wikidata.org/wiki/Q899157","display_name":"Hydrophobic effect","level":2,"score":0.3228999972343445},{"id":"https://openalex.org/C107824862","wikidata":"https://www.wikidata.org/wiki/Q616005","display_name":"Binding site","level":2,"score":0.30559998750686646},{"id":"https://openalex.org/C32909587","wikidata":"https://www.wikidata.org/wiki/Q11369","display_name":"Molecule","level":2,"score":0.290800005197525},{"id":"https://openalex.org/C116073593","wikidata":"https://www.wikidata.org/wiki/Q864491","display_name":"Biological activity","level":3,"score":0.2906999886035919},{"id":"https://openalex.org/C99679407","wikidata":"https://www.wikidata.org/wiki/Q56761637","display_name":"Substructure","level":2,"score":0.2831999957561493},{"id":"https://openalex.org/C2776608144","wikidata":"https://www.wikidata.org/wiki/Q410352","display_name":"Gabapentin","level":3,"score":0.265500009059906},{"id":"https://openalex.org/C74998103","wikidata":"https://www.wikidata.org/wiki/Q898254","display_name":"Dissociation constant","level":3,"score":0.26269999146461487},{"id":"https://openalex.org/C12554922","wikidata":"https://www.wikidata.org/wiki/Q7100","display_name":"Biophysics","level":1,"score":0.2619999945163727},{"id":"https://openalex.org/C21951064","wikidata":"https://www.wikidata.org/wiki/Q899212","display_name":"Combinatorial chemistry","level":1,"score":0.2522999942302704}],"mesh":[{"descriptor_ui":"D001643","descriptor_name":"Bridged Bicyclo Compounds","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D001643","descriptor_name":"Bridged Bicyclo Compounds","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D001643","descriptor_name":"Bridged Bicyclo Compounds","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D001643","descriptor_name":"Bridged Bicyclo Compounds","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D001643","descriptor_name":"Bridged Bicyclo Compounds","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D001643","descriptor_name":"Bridged Bicyclo Compounds","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D001643","descriptor_name":"Bridged Bicyclo Compounds","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D001643","descriptor_name":"Bridged Bicyclo Compounds","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D001643","descriptor_name":"Bridged Bicyclo Compounds","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D001643","descriptor_name":"Bridged Bicyclo Compounds","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D001643","descriptor_name":"Bridged Bicyclo Compounds","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D001643","descriptor_name":"Bridged Bicyclo Compounds","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"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":"D015220","descriptor_name":"Calcium Channels","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D015220","descriptor_name":"Calcium Channels","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D015220","descriptor_name":"Calcium Channels","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D015220","descriptor_name":"Calcium Channels","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D015220","descriptor_name":"Calcium Channels","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D015220","descriptor_name":"Calcium Channels","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D015220","descriptor_name":"Calcium Channels","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D015220","descriptor_name":"Calcium Channels","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D056004","descriptor_name":"Molecular Dynamics Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D056004","descriptor_name":"Molecular Dynamics Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D056004","descriptor_name":"Molecular Dynamics Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D056004","descriptor_name":"Molecular Dynamics Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D062105","descriptor_name":"Molecular Docking Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D062105","descriptor_name":"Molecular Docking Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D062105","descriptor_name":"Molecular Docking Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D062105","descriptor_name":"Molecular Docking Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":3,"locations":[{"id":"doi:10.1021/acs.jcim.5c02583","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.5c02583","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":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Chemical Information and Modeling","raw_type":"journal-article"},{"id":"pmid:41439594","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/41439594","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:12802839","is_oa":true,"landing_page_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12802839/","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"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":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"J Chem Inf Model","raw_type":"Text"}],"best_oa_location":{"id":"pmh:oai:pubmedcentral.nih.gov:12802839","is_oa":true,"landing_page_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12802839/","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"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":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"J Chem Inf Model","raw_type":"Text"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/7","display_name":"Affordable and clean energy","score":0.8236562609672546}],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":58,"referenced_works":["https://openalex.org/W1031578623","https://openalex.org/W1600089255","https://openalex.org/W1968984443","https://openalex.org/W2015688756","https://openalex.org/W2029667189","https://openalex.org/W2061108756","https://openalex.org/W2069123478","https://openalex.org/W2081280346","https://openalex.org/W2084567915","https://openalex.org/W2085295826","https://openalex.org/W2091392856","https://openalex.org/W2124026197","https://openalex.org/W2126529674","https://openalex.org/W2137825366","https://openalex.org/W2142868265","https://openalex.org/W2147993766","https://openalex.org/W2207535250","https://openalex.org/W2281340876","https://openalex.org/W2343614482","https://openalex.org/W2411729015","https://openalex.org/W2469235540","https://openalex.org/W2587625522","https://openalex.org/W2620712420","https://openalex.org/W2791425968","https://openalex.org/W2901386532","https://openalex.org/W2912056231","https://openalex.org/W2917833092","https://openalex.org/W3035815479","https://openalex.org/W3103588515","https://openalex.org/W3111048666","https://openalex.org/W3113449051","https://openalex.org/W3178563513","https://openalex.org/W3198320390","https://openalex.org/W3202287440","https://openalex.org/W3208589454","https://openalex.org/W4214815742","https://openalex.org/W4224930335","https://openalex.org/W4292423764","https://openalex.org/W4309679168","https://openalex.org/W4310785556","https://openalex.org/W4318706909","https://openalex.org/W4327558553","https://openalex.org/W4360999579","https://openalex.org/W4376109039","https://openalex.org/W4376878571","https://openalex.org/W4387440676","https://openalex.org/W4388696029","https://openalex.org/W4392458799","https://openalex.org/W4393176157","https://openalex.org/W4393343312","https://openalex.org/W4396814801","https://openalex.org/W4400604626","https://openalex.org/W4406274436","https://openalex.org/W4408293149","https://openalex.org/W4409986801","https://openalex.org/W4410225196","https://openalex.org/W4410409223","https://openalex.org/W4412137501"],"related_works":[],"abstract_inverted_index":{"Crisugabalin,":[0],"a":[1,8,218,258,269],"recently":[2],"approved":[3],"third-generation":[4],"GABA":[5],"analogue":[6],"with":[7,297],"unique":[9,235],"cage-like":[10,241,254],"tricyclic":[11,242,255],"scaffold,":[12,243],"shows":[13],"superior":[14,96],"efficacy":[15],"and":[16,20,30,69,90,105,113,163,166,182,195,200,228,266,279],"safety":[17],"over":[18,103],"pregabalin":[19,142,181],"mirogabalin":[21],"for":[22,66,87,99,180,185,192,271,289,294],"treating":[23],"neuropathic":[24],"pain.":[25],"Through":[26],"integrated":[27],"biophysical,":[28],"structural,":[29],"computational":[31,287],"approaches,":[32],"we":[33],"elucidate":[34],"the":[35,50,55,72,76,120,160,171,188,209,253],"molecular":[36],"basis":[37],"of":[38,119,177,208],"its":[39,240],"enhanced":[40,110,223],"pharmacological":[41],"profile.":[42],"Dissociation":[43],"kinetic":[44],"studies":[45],"revealed":[46,150,214],"that":[47,151,215,261],"crisugabalin":[48,136,196,216],"exhibited":[49],"slowest":[51],"dissociation":[52,74,153],"kinetics":[53],"from":[54,75,239],"\u03b1":[56,77,100],"2":[57,78,101],"\u03b41":[58,102],"subunit":[59,80],"(\u03c4":[60,81],"=":[61,82],"32.05,":[62],"80.00,":[63],"111.11":[64],"min":[65,86],"pregabalin,":[67,88,193],"mirogabalin,":[68,89,194],"crisugabalin)":[70],"but":[71],"fastest":[73],"\u03b42":[79],"8.70,":[83],"16.39,":[84],"5.78":[85],"crisugabalin).":[91],"Cryo-EM":[92],"structures":[93],"demonstrated":[94],"crisugabalin\u2019s":[95],"binding":[97,123,189,210,236,264],"affinity":[98],"gabapentin":[104],"l":[106,121],"-leucine,":[107],"driven":[108],"by":[109,135,204,222],"hydrogen":[111,133],"bonding":[112,134],"hydrophobic":[114,224],"contacts,":[115],"alongside":[116],"volumetric":[117],"expansion":[118],"-leucine":[122],"pocket.":[124],"Molecular":[125,146],"dynamics":[126],"(MD)":[127],"simulations":[128,149],"identified":[129],"significantly":[130],"more":[131],"persistent":[132],"(66.3%":[137],"average":[138],"occupancy)":[139],"relative":[140],"to":[141],"(28.3%).":[143],"Random":[144],"Acceleration":[145],"Dynamics":[147],"(RAMD)":[148],"ligand":[152,172],"primarily":[154],"proceeds":[155],"via":[156],"Pathway":[157],"A":[158],"(along":[159],"\u03b22,":[161],"\u03b23,":[162],"\u03b21":[164],"segments),":[165],"\u03c4RAMD":[167],"calculations":[168],"correctly":[169],"ranked":[170],"residence":[173,300],"times,":[174],"yielding":[175],"values":[176],"0.18":[178],"ns":[179,184],"2.88":[183],"crisugabalin.":[186],"Furthermore,":[187],"free":[190,211],"energies":[191],"were":[197],"\u221221.64,":[198],"\u221231.30,":[199],"\u221234.99":[201],"kcal/mol,":[202],"calculated":[203],"MM/GBSA.":[205],"The":[206],"decomposition":[207],"energy":[212],"components":[213],"exhibits":[217],"dual-action":[219],"mechanism":[220],"characterized":[221],"interactions":[225],"(\u221228.46":[226],"kcal/mol)":[227],"favorable":[229],"entropic":[230],"contributions":[231],"(3.03":[232],"kcal/mol).":[233],"This":[234],"behavior":[237],"stems":[238],"an":[244],"unprecedented":[245],"substructure":[246],"in":[247,282],"drug":[248,291],"molecules.":[249],"These":[250],"findings":[251],"establish":[252],"motif":[256],"as":[257],"novel":[259],"pharmacophore":[260],"simultaneously":[262],"optimizes":[263],"entropy":[265],"enthalpy,":[267],"providing":[268],"blueprint":[270],"next-generation":[272],"voltage-gated":[273],"calcium":[274],"channel":[275],"modulators.":[276],"MD,":[277],"\u03c4RAMD,":[278],"MM-GBSA":[280],"used":[281],"this":[283],"study":[284],"are":[285],"powerful":[286],"tools":[288],"rational":[290],"design,":[292],"particularly":[293],"optimizing":[295],"compounds":[296],"prolonged":[298],"target":[299],"times.":[301]},"counts_by_year":[{"year":2026,"cited_by_count":1}],"updated_date":"2026-06-15T08:34:33.830935","created_date":"2025-12-24T00:00:00"}
