{"id":"https://openalex.org/W7169559271","doi":"https://doi.org/10.1021/acs.jctc.6c01079","title":"Efficient Force Evaluation via Fragmentation: Toward Geometry Optimization of Protein\u2013Ligand Systems with Quantum Mechanical Accuracy","display_name":"Efficient Force Evaluation via Fragmentation: Toward Geometry Optimization of Protein\u2013Ligand Systems with Quantum Mechanical Accuracy","publication_year":2026,"publication_date":"2026-07-17","ids":{"openalex":"https://openalex.org/W7169559271","doi":"https://doi.org/10.1021/acs.jctc.6c01079","pmid":"https://pubmed.ncbi.nlm.nih.gov/42466991"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jctc.6c01079","doi":"https://doi.org/10.1021/acs.jctc.6c01079","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jctc.6c01079","pdf_url":null,"source":{"id":"https://openalex.org/S189701308","display_name":"Journal of Chemical Theory and Computation","issn_l":"1549-9618","issn":["1549-9618","1549-9626"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","jufo-2","ki-jl-2","medline","norway-2"],"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 Theory and Computation","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5101463940","display_name":"Ruocheng Han","orcid":"https://orcid.org/0000-0001-9874-9965","observed_orcids":["https://orcid.org/0000-0001-9874-9965"]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Ruocheng Han","raw_affiliation_strings":["Independent Researcher , ,"],"raw_orcid":"https://orcid.org/0000-0001-9874-9965","affiliations":[{"raw_affiliation_string":"Independent Researcher , ,","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5064467467","display_name":"Zonghua Bo","orcid":"https://orcid.org/0000-0003-4728-2968","observed_orcids":["https://orcid.org/0000-0003-4728-2968"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Zonghua Bo","raw_affiliation_strings":["Independent Researcher , ,"],"raw_orcid":"https://orcid.org/0000-0003-4728-2968","affiliations":[{"raw_affiliation_string":"Independent Researcher , ,","institution_ids":[]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5028313304","display_name":"Jiawei Yan","orcid":"https://orcid.org/0000-0002-3446-7042","observed_orcids":["https://orcid.org/0000-0002-3446-7042","https://orcid.org/0009-0008-0763-7457"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Jiawei Yan","raw_affiliation_strings":["Independent Researcher , ,"],"raw_orcid":"https://orcid.org/0000-0002-3446-7042","affiliations":[{"raw_affiliation_string":"Independent Researcher , ,","institution_ids":[]}]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":["https://openalex.org/A5101463940"],"corresponding_institution_ids":[],"apc_list":{"value":4500,"currency":"USD","value_usd":4500},"apc_paid":null,"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.54172576,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"22","issue":"16","first_page":"8669","last_page":"8681"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10002","display_name":"Advanced Chemical Physics Studies","score":0.9599999785423279,"subfield":{"id":"https://openalex.org/subfields/3107","display_name":"Atomic and Molecular Physics, and Optics"},"field":{"id":"https://openalex.org/fields/31","display_name":"Physics and Astronomy"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},"topics":[{"id":"https://openalex.org/T10002","display_name":"Advanced Chemical Physics Studies","score":0.9599999785423279,"subfield":{"id":"https://openalex.org/subfields/3107","display_name":"Atomic and Molecular Physics, and Optics"},"field":{"id":"https://openalex.org/fields/31","display_name":"Physics and Astronomy"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T10211","display_name":"Computational Drug Discovery Methods","score":0.03500000014901161,"subfield":{"id":"https://openalex.org/subfields/1703","display_name":"Computational Theory and Mathematics"},"field":{"id":"https://openalex.org/fields/17","display_name":"Computer Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T12044","display_name":"Advanced Physical and Chemical Molecular Interactions","score":0.0019000000320374966,"subfield":{"id":"https://openalex.org/subfields/1606","display_name":"Physical and Theoretical Chemistry"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/force-evaluation","display_name":"force evaluation","score":0.5839999914169312},{"id":"https://openalex.org/keywords/molecular-fragmentation","display_name":"molecular fragmentation","score":0.7839999794960022},{"id":"https://openalex.org/keywords/protein-ligand-complex","display_name":"protein-ligand complex","score":0.8539999723434448},{"id":"https://openalex.org/keywords/geometric-optimization","display_name":"geometry optimization","score":0.9869999885559082},{"id":"https://openalex.org/keywords/interatomic-forces","display_name":"interatomic forces","score":0.8270000219345093},{"id":"https://openalex.org/keywords/interaction-energy","display_name":"interaction energy","score":0.7850000262260437},{"id":"https://openalex.org/keywords/gfn2-xtb","display_name":"GFN2-xTB","score":0.8960000276565552},{"id":"https://openalex.org/keywords/semiempirical-quantum-mechanics","display_name":"semiempirical quantum mechanics","score":0.8429999947547913},{"id":"https://openalex.org/keywords/molecular-mechanics","display_name":"molecular mechanics","score":0.703000009059906},{"id":"https://openalex.org/keywords/hydrogen-bond-network","display_name":"hydrogen bond network","score":0.7670000195503235},{"id":"https://openalex.org/keywords/structure-activity-relationship","display_name":"structure-activity relationship","score":0.7730000019073486},{"id":"https://openalex.org/keywords/computational-efficiency","display_name":"computational efficiency","score":0.5799999833106995}],"concepts":[{"id":"https://openalex.org/C166950319","wikidata":"https://www.wikidata.org/wiki/Q245031","display_name":"Intermolecular force","level":3,"score":0.6762999892234802},{"id":"https://openalex.org/C75079739","wikidata":"https://www.wikidata.org/wiki/Q1571801","display_name":"Intramolecular force","level":2,"score":0.641700029373169},{"id":"https://openalex.org/C84114770","wikidata":"https://www.wikidata.org/wiki/Q46344","display_name":"Quantum","level":2,"score":0.6122999787330627},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.5695000290870667},{"id":"https://openalex.org/C10803110","wikidata":"https://www.wikidata.org/wiki/Q1341441","display_name":"Force field (fiction)","level":2,"score":0.5529000163078308},{"id":"https://openalex.org/C14961307","wikidata":"https://www.wikidata.org/wiki/Q5377176","display_name":"Energy minimization","level":2,"score":0.5266000032424927},{"id":"https://openalex.org/C204323151","wikidata":"https://www.wikidata.org/wiki/Q905424","display_name":"Range (aeronautics)","level":2,"score":0.5232999920845032},{"id":"https://openalex.org/C121864883","wikidata":"https://www.wikidata.org/wiki/Q677916","display_name":"Statistical physics","level":1,"score":0.421999990940094},{"id":"https://openalex.org/C121332964","wikidata":"https://www.wikidata.org/wiki/Q413","display_name":"Physics","level":0,"score":0.37880000472068787},{"id":"https://openalex.org/C20803032","wikidata":"https://www.wikidata.org/wiki/Q207900","display_name":"QM/MM","level":3,"score":0.36980000138282776},{"id":"https://openalex.org/C59593255","wikidata":"https://www.wikidata.org/wiki/Q901663","display_name":"Molecular dynamics","level":2,"score":0.3596999943256378},{"id":"https://openalex.org/C2991951333","wikidata":"https://www.wikidata.org/wiki/Q188403","display_name":"Quantum chemical","level":3,"score":0.34310001134872437},{"id":"https://openalex.org/C74650414","wikidata":"https://www.wikidata.org/wiki/Q11397","display_name":"Classical mechanics","level":1,"score":0.3393999934196472},{"id":"https://openalex.org/C79745364","wikidata":"https://www.wikidata.org/wiki/Q190663","display_name":"Central force","level":2,"score":0.328000009059906},{"id":"https://openalex.org/C135694725","wikidata":"https://www.wikidata.org/wiki/Q1201087","display_name":"Detailed balance","level":2,"score":0.3215999901294708},{"id":"https://openalex.org/C2989255885","wikidata":"https://www.wikidata.org/wiki/Q500256","display_name":"Molecular conformation","level":3,"score":0.31859999895095825},{"id":"https://openalex.org/C11413529","wikidata":"https://www.wikidata.org/wiki/Q8366","display_name":"Algorithm","level":1,"score":0.30550000071525574},{"id":"https://openalex.org/C193547582","wikidata":"https://www.wikidata.org/wiki/Q911331","display_name":"Molecular geometry","level":3,"score":0.2953999936580658},{"id":"https://openalex.org/C126298732","wikidata":"https://www.wikidata.org/wiki/Q1371892","display_name":"Structural mechanics","level":3,"score":0.2777999937534332},{"id":"https://openalex.org/C147764199","wikidata":"https://www.wikidata.org/wiki/Q6865248","display_name":"Minification","level":2,"score":0.2671000063419342},{"id":"https://openalex.org/C84551667","wikidata":"https://www.wikidata.org/wiki/Q155640","display_name":"Potential energy","level":2,"score":0.265500009059906},{"id":"https://openalex.org/C459310","wikidata":"https://www.wikidata.org/wiki/Q117801","display_name":"Computational science","level":1,"score":0.26350000500679016}],"mesh":[{"descriptor_ui":"D000098222","descriptor_name":"Quantum Mechanics","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D006860","descriptor_name":"Hydrogen Bonding","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":"D011506","descriptor_name":"Proteins","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D011506","descriptor_name":"Proteins","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D011789","descriptor_name":"Quantum Theory","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":false}],"locations_count":2,"locations":[{"id":"doi:10.1021/acs.jctc.6c01079","doi":"https://doi.org/10.1021/acs.jctc.6c01079","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jctc.6c01079","pdf_url":null,"source":{"id":"https://openalex.org/S189701308","display_name":"Journal of Chemical Theory and Computation","issn_l":"1549-9618","issn":["1549-9618","1549-9626"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","jufo-2","ki-jl-2","medline","norway-2"],"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 Theory and Computation","raw_type":"journal-article"},{"id":"pmid:42466991","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/42466991","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,"listed_in":[],"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 theory and computation","raw_type":"Journal Article"}],"best_oa_location":null,"sustainable_development_goals":[],"sustainable_development_goals_aurora":[],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":78,"referenced_works":["https://openalex.org/W933796449","https://openalex.org/W1695379209","https://openalex.org/W1965425135","https://openalex.org/W1966182950","https://openalex.org/W1968166922","https://openalex.org/W1971572370","https://openalex.org/W1971699116","https://openalex.org/W1972458893","https://openalex.org/W1975845692","https://openalex.org/W1983598802","https://openalex.org/W1984007963","https://openalex.org/W1988636074","https://openalex.org/W2005136695","https://openalex.org/W2019857898","https://openalex.org/W2022696619","https://openalex.org/W2031694014","https://openalex.org/W2032084435","https://openalex.org/W2033777798","https://openalex.org/W2038210983","https://openalex.org/W2043929927","https://openalex.org/W2051370579","https://openalex.org/W2057594036","https://openalex.org/W2061013558","https://openalex.org/W2062653920","https://openalex.org/W2069924395","https://openalex.org/W2074386125","https://openalex.org/W2078409719","https://openalex.org/W2078432797","https://openalex.org/W2080384673","https://openalex.org/W2092157292","https://openalex.org/W2094423707","https://openalex.org/W2095148640","https://openalex.org/W2103111465","https://openalex.org/W2110872379","https://openalex.org/W2111278964","https://openalex.org/W2111533830","https://openalex.org/W2118622794","https://openalex.org/W2133986308","https://openalex.org/W2137107720","https://openalex.org/W2169678694","https://openalex.org/W2169858698","https://openalex.org/W2323519269","https://openalex.org/W2323562486","https://openalex.org/W2325904293","https://openalex.org/W2335804930","https://openalex.org/W2346422904","https://openalex.org/W2552525540","https://openalex.org/W2563108390","https://openalex.org/W2605801743","https://openalex.org/W2613905013","https://openalex.org/W2749311864","https://openalex.org/W2756519801","https://openalex.org/W2761786744","https://openalex.org/W2762627974","https://openalex.org/W2767688229","https://openalex.org/W2786827898","https://openalex.org/W2799609624","https://openalex.org/W2800381444","https://openalex.org/W2801937020","https://openalex.org/W2911997094","https://openalex.org/W3007178273","https://openalex.org/W3013002235","https://openalex.org/W3197886297","https://openalex.org/W4224236177","https://openalex.org/W4236137384","https://openalex.org/W4319457850","https://openalex.org/W4366236977","https://openalex.org/W4387310362","https://openalex.org/W4391560080","https://openalex.org/W4404906120","https://openalex.org/W4406017803","https://openalex.org/W4406030349","https://openalex.org/W4406056388","https://openalex.org/W4407388305","https://openalex.org/W4409170662","https://openalex.org/W4409293785","https://openalex.org/W4409901056","https://openalex.org/W4411571563"],"related_works":[],"abstract_inverted_index":{"Accurate":[0],"evaluation":[1,85],"of":[2,25,66,134],"interatomic":[3],"forces":[4,104],"and":[5,30,40,82,163],"interaction":[6,122],"energies":[7],"in":[8,27],"large":[9,87],"molecular":[10,88,108],"systems,":[11],"such":[12],"as":[13],"protein-ligand":[14,127],"complexes":[15],"or":[16],"polymer-molecule":[17],"assemblies,":[18],"is":[19],"essential":[20,121],"for":[21,86],"a":[22,35,43,74,132],"wide":[23],"range":[24],"applications":[26],"drug":[28],"discovery":[29],"materials":[31],"science.":[32],"However,":[33],"achieving":[34],"balance":[36],"between":[37],"computational":[38],"efficiency":[39],"accuracy":[41,62],"remains":[42],"major":[44],"challenge:":[45],"classical":[46],"force":[47,84],"fields":[48],"offer":[49],"high":[50],"speed":[51],"but":[52],"limited":[53],"precision,":[54],"while":[55,102,118],"quantum":[56],"mechanical":[57],"(QM)":[58],"methods":[59],"provide":[60],"greater":[61],"at":[63,96],"the":[64,97,120,129,146,160,165],"cost":[65],"poor":[67],"scalability.":[68],"In":[69],"this":[70],"work,":[71],"we":[72],"present":[73],"hybrid":[75],"fragmentation-based":[76],"approach,":[77],"FragQMMM,":[78],"that":[79],"enables":[80],"efficient":[81],"accurate":[83],"systems.":[89],"Specifically,":[90],"crucial":[91],"intermolecular":[92],"interactions":[93],"are":[94,105],"treated":[95],"semiempirical":[98],"QM":[99,140,148],"level":[100],"(GFN2-xTB),":[101],"intramolecular":[103],"described":[106],"using":[107],"mechanics":[109],"(MM).":[110],"This":[111],"selective":[112],"treatment":[113],"greatly":[114],"accelerates":[115],"geometry":[116],"optimization":[117],"preserving":[119,164],"features.":[123],"When":[124],"applied":[125],"to":[126,138],"complexes,":[128],"method":[130],"delivers":[131],"speed-up":[133],"roughly":[135],"10-100\u00d7":[136],"compared":[137],"full":[139],"calculations.":[141],"The":[142],"resulting":[143],"geometries":[144],"match":[145],"reference":[147],"structures":[149],"more":[150],"closely":[151],"than":[152],"those":[153],"obtained":[154],"with":[155],"pure":[156],"MM,":[157],"successfully":[158],"reproducing":[159],"hydrogen-bond":[161],"network":[162],"underlying":[166],"structure-activity":[167],"relationship.":[168]},"counts_by_year":[],"updated_date":"2026-10-02T10:15:12.560889","created_date":"2026-07-18T00:00:00"}