{"id":"https://openalex.org/W2206257966","doi":"https://doi.org/10.1021/acs.jcim.5b00621","title":"Impact of Surface Water Layers on Protein\u2013Ligand Binding: How Well Are Experimental Data Reproduced by Molecular Dynamics Simulations in a Thermolysin Test Case?","display_name":"Impact of Surface Water Layers on Protein\u2013Ligand Binding: How Well Are Experimental Data Reproduced by Molecular Dynamics Simulations in a Thermolysin Test Case?","publication_year":2015,"publication_date":"2015-12-21","ids":{"openalex":"https://openalex.org/W2206257966","doi":"https://doi.org/10.1021/acs.jcim.5b00621","mag":"2206257966","pmid":"https://pubmed.ncbi.nlm.nih.gov/26691064"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.5b00621","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.5b00621","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":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5003816391","display_name":"Michael Betz","orcid":"https://orcid.org/0000-0002-9837-9180"},"institutions":[{"id":"https://openalex.org/I161103922","display_name":"Philipps University of Marburg","ror":"https://ror.org/01rdrb571","country_code":"DE","type":"education","lineage":["https://openalex.org/I161103922"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Michael Betz","raw_affiliation_strings":["Department of Pharmaceutical\rChemistry, Philipps-University Marburg, Marbacher Weg 6, 35032 Marburg, Germany"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pharmaceutical\rChemistry, Philipps-University Marburg, Marbacher Weg 6, 35032 Marburg, Germany","institution_ids":["https://openalex.org/I161103922"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5110290307","display_name":"Tobias Wulsdorf","orcid":null},"institutions":[{"id":"https://openalex.org/I161103922","display_name":"Philipps University of Marburg","ror":"https://ror.org/01rdrb571","country_code":"DE","type":"education","lineage":["https://openalex.org/I161103922"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Tobias Wulsdorf","raw_affiliation_strings":["Department of Pharmaceutical\rChemistry, Philipps-University Marburg, Marbacher Weg 6, 35032 Marburg, Germany"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pharmaceutical\rChemistry, Philipps-University Marburg, Marbacher Weg 6, 35032 Marburg, Germany","institution_ids":["https://openalex.org/I161103922"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5027768829","display_name":"S.G. Krimmer","orcid":"https://orcid.org/0000-0002-5669-9071"},"institutions":[{"id":"https://openalex.org/I161103922","display_name":"Philipps University of Marburg","ror":"https://ror.org/01rdrb571","country_code":"DE","type":"education","lineage":["https://openalex.org/I161103922"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Stefan G. Krimmer","raw_affiliation_strings":["Department of Pharmaceutical\rChemistry, Philipps-University Marburg, Marbacher Weg 6, 35032 Marburg, Germany"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pharmaceutical\rChemistry, Philipps-University Marburg, Marbacher Weg 6, 35032 Marburg, Germany","institution_ids":["https://openalex.org/I161103922"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5005420915","display_name":"G. Klebe","orcid":"https://orcid.org/0000-0002-4913-390X"},"institutions":[{"id":"https://openalex.org/I161103922","display_name":"Philipps University of Marburg","ror":"https://ror.org/01rdrb571","country_code":"DE","type":"education","lineage":["https://openalex.org/I161103922"]}],"countries":["DE"],"is_corresponding":true,"raw_author_name":"Gerhard Klebe","raw_affiliation_strings":["Department of Pharmaceutical\rChemistry, Philipps-University Marburg, Marbacher Weg 6, 35032 Marburg, Germany"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pharmaceutical\rChemistry, Philipps-University Marburg, Marbacher Weg 6, 35032 Marburg, Germany","institution_ids":["https://openalex.org/I161103922"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":4,"corresponding_author_ids":["https://openalex.org/A5005420915"],"corresponding_institution_ids":["https://openalex.org/I161103922"],"apc_list":null,"apc_paid":null,"fwci":2.2592,"has_fulltext":false,"cited_by_count":38,"citation_normalized_percentile":{"value":0.88449825,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":89,"max":99},"biblio":{"volume":"56","issue":"1","first_page":"223","last_page":"233"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10044","display_name":"Protein Structure and Dynamics","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/T10044","display_name":"Protein Structure and Dynamics","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/T11162","display_name":"Enzyme Structure and Function","score":0.9991999864578247,"subfield":{"id":"https://openalex.org/subfields/2505","display_name":"Materials Chemistry"},"field":{"id":"https://openalex.org/fields/25","display_name":"Materials Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T11177","display_name":"Spectroscopy and Quantum Chemical Studies","score":0.9980999827384949,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/solvation","display_name":"Solvation","score":0.8327927589416504},{"id":"https://openalex.org/keywords/thermolysin","display_name":"Thermolysin","score":0.7232134342193604},{"id":"https://openalex.org/keywords/molecular-dynamics","display_name":"Molecular dynamics","score":0.686219334602356},{"id":"https://openalex.org/keywords/chemistry","display_name":"Chemistry","score":0.6781579256057739},{"id":"https://openalex.org/keywords/ligand","display_name":"Ligand (biochemistry)","score":0.5311583280563354},{"id":"https://openalex.org/keywords/chemical-physics","display_name":"Chemical physics","score":0.5048323273658752},{"id":"https://openalex.org/keywords/solvation-shell","display_name":"Solvation shell","score":0.44699278473854065},{"id":"https://openalex.org/keywords/enthalpy","display_name":"Enthalpy","score":0.42250463366508484},{"id":"https://openalex.org/keywords/computational-chemistry","display_name":"Computational chemistry","score":0.34914299845695496},{"id":"https://openalex.org/keywords/crystallography","display_name":"Crystallography","score":0.32932960987091064},{"id":"https://openalex.org/keywords/molecule","display_name":"Molecule","score":0.2622079849243164},{"id":"https://openalex.org/keywords/thermodynamics","display_name":"Thermodynamics","score":0.18709325790405273},{"id":"https://openalex.org/keywords/receptor","display_name":"Receptor","score":0.09157580137252808},{"id":"https://openalex.org/keywords/organic-chemistry","display_name":"Organic chemistry","score":0.07008752226829529}],"concepts":[{"id":"https://openalex.org/C148093993","wikidata":"https://www.wikidata.org/wiki/Q739398","display_name":"Solvation","level":3,"score":0.8327927589416504},{"id":"https://openalex.org/C185020521","wikidata":"https://www.wikidata.org/wiki/Q409163","display_name":"Thermolysin","level":4,"score":0.7232134342193604},{"id":"https://openalex.org/C59593255","wikidata":"https://www.wikidata.org/wiki/Q901663","display_name":"Molecular dynamics","level":2,"score":0.686219334602356},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.6781579256057739},{"id":"https://openalex.org/C116569031","wikidata":"https://www.wikidata.org/wiki/Q899107","display_name":"Ligand (biochemistry)","level":3,"score":0.5311583280563354},{"id":"https://openalex.org/C159467904","wikidata":"https://www.wikidata.org/wiki/Q2001702","display_name":"Chemical physics","level":1,"score":0.5048323273658752},{"id":"https://openalex.org/C149823470","wikidata":"https://www.wikidata.org/wiki/Q1088326","display_name":"Solvation shell","level":4,"score":0.44699278473854065},{"id":"https://openalex.org/C3288061","wikidata":"https://www.wikidata.org/wiki/Q161064","display_name":"Enthalpy","level":2,"score":0.42250463366508484},{"id":"https://openalex.org/C147597530","wikidata":"https://www.wikidata.org/wiki/Q369472","display_name":"Computational chemistry","level":1,"score":0.34914299845695496},{"id":"https://openalex.org/C8010536","wikidata":"https://www.wikidata.org/wiki/Q160398","display_name":"Crystallography","level":1,"score":0.32932960987091064},{"id":"https://openalex.org/C32909587","wikidata":"https://www.wikidata.org/wiki/Q11369","display_name":"Molecule","level":2,"score":0.2622079849243164},{"id":"https://openalex.org/C97355855","wikidata":"https://www.wikidata.org/wiki/Q11473","display_name":"Thermodynamics","level":1,"score":0.18709325790405273},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.09157580137252808},{"id":"https://openalex.org/C178790620","wikidata":"https://www.wikidata.org/wiki/Q11351","display_name":"Organic chemistry","level":1,"score":0.07008752226829529},{"id":"https://openalex.org/C2780340462","wikidata":"https://www.wikidata.org/wiki/Q127450","display_name":"Trypsin","level":3,"score":0.0},{"id":"https://openalex.org/C121332964","wikidata":"https://www.wikidata.org/wiki/Q413","display_name":"Physics","level":0,"score":0.0},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.0},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.0}],"mesh":[{"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":"D011485","descriptor_name":"Protein Binding","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011485","descriptor_name":"Protein Binding","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011485","descriptor_name":"Protein Binding","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011487","descriptor_name":"Protein Conformation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011487","descriptor_name":"Protein Conformation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011487","descriptor_name":"Protein Conformation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D013329","descriptor_name":"Structure-Activity Relationship","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D013329","descriptor_name":"Structure-Activity Relationship","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D013329","descriptor_name":"Structure-Activity Relationship","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D013816","descriptor_name":"Thermodynamics","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D013816","descriptor_name":"Thermodynamics","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D013816","descriptor_name":"Thermodynamics","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D013820","descriptor_name":"Thermolysin","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D013820","descriptor_name":"Thermolysin","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D013820","descriptor_name":"Thermolysin","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D013820","descriptor_name":"Thermolysin","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D013820","descriptor_name":"Thermolysin","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D013820","descriptor_name":"Thermolysin","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D014867","descriptor_name":"Water","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D014867","descriptor_name":"Water","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D014867","descriptor_name":"Water","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D015195","descriptor_name":"Drug Design","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015195","descriptor_name":"Drug Design","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015195","descriptor_name":"Drug Design","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015203","descriptor_name":"Reproducibility of Results","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015203","descriptor_name":"Reproducibility of Results","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015203","descriptor_name":"Reproducibility of Results","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":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":2,"locations":[{"id":"doi:10.1021/acs.jcim.5b00621","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.5b00621","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:26691064","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/26691064","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}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Clean water and sanitation","id":"https://metadata.un.org/sdg/6","score":0.8500000238418579}],"awards":[{"id":"https://openalex.org/G6844625903","display_name":null,"funder_award_id":"268145","funder_id":"https://openalex.org/F4320334678","funder_display_name":"European Research Council"}],"funders":[{"id":"https://openalex.org/F4320334678","display_name":"European Research Council","ror":"https://ror.org/0472cxd90"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":37,"referenced_works":["https://openalex.org/W1974818478","https://openalex.org/W1976161355","https://openalex.org/W1976499671","https://openalex.org/W1980337077","https://openalex.org/W1994938913","https://openalex.org/W1998048173","https://openalex.org/W2010499880","https://openalex.org/W2015688756","https://openalex.org/W2024726841","https://openalex.org/W2029667189","https://openalex.org/W2029743552","https://openalex.org/W2032665736","https://openalex.org/W2032842297","https://openalex.org/W2039127550","https://openalex.org/W2044797251","https://openalex.org/W2047115921","https://openalex.org/W2055205961","https://openalex.org/W2058698413","https://openalex.org/W2061097764","https://openalex.org/W2065856326","https://openalex.org/W2070206101","https://openalex.org/W2074076945","https://openalex.org/W2077212468","https://openalex.org/W2081719547","https://openalex.org/W2086190523","https://openalex.org/W2087596773","https://openalex.org/W2092358128","https://openalex.org/W2106140689","https://openalex.org/W2114822683","https://openalex.org/W2147993766","https://openalex.org/W2151319417","https://openalex.org/W2151884301","https://openalex.org/W2154063883","https://openalex.org/W2162027701","https://openalex.org/W2180229411","https://openalex.org/W2314067773","https://openalex.org/W4238642012"],"related_works":["https://openalex.org/W2070679687","https://openalex.org/W2040663074","https://openalex.org/W2055804837","https://openalex.org/W2042366629","https://openalex.org/W2018648187","https://openalex.org/W4242247773","https://openalex.org/W3175840220","https://openalex.org/W2009325851","https://openalex.org/W4231356318","https://openalex.org/W2579471528"],"abstract_inverted_index":{"Drug":[0],"binding":[1,45,59],"involves":[2],"changes":[3],"of":[4,32,39,57,76,146],"the":[5,24,40,58,72,77,83,90,108,130],"local":[6],"water":[7,12,79,101],"structure":[8],"around":[9,17,82,107],"proteins":[10],"including":[11],"rearrangements":[13],"across":[14],"surface-solvation":[15],"layers":[16],"protein":[18],"and":[19,74,103,143],"ligand":[20],"portions":[21],"exposed":[22,42],"to":[23,48,98,136],"newly":[25],"formed":[26,84],"complex":[27],"surface.":[28],"For":[29],"a":[30],"series":[31],"thermolysin-binding":[33],"phosphonamidates,":[34],"we":[35],"discovered":[36],"that":[37],"variations":[38],"partly":[41],"P2'-substituents":[43],"modulate":[44],"affinity":[46],"up":[47],"10":[49],"kJ":[50],"mol(-1)":[51],"with":[52,114,129],"even":[53],"larger":[54],"enthalpy/entropy":[55],"partitioning":[56],"signature.":[60],"The":[61],"observed":[62,91],"profiles":[63],"cannot":[64],"be":[65],"completely":[66],"explained":[67],"by":[68,141],"desolvation":[69],"effects.":[70],"Instead,":[71],"quality":[73],"completeness":[75],"surface":[78,100],"network":[80],"wrapping":[81],"complexes":[85],"provide":[86],"an":[87],"explanation":[88],"for":[89],"structure-activity":[92],"relationship.":[93],"We":[94],"used":[95],"molecular":[96],"dynamics":[97],"compute":[99],"networks":[102],"predict":[104],"solvation":[105],"sites":[106],"complexes.":[109],"A":[110],"fairly":[111],"good":[112],"correspondence":[113],"experimental":[115],"difference":[116],"electron":[117],"densities":[118],"in":[119,125],"high-resolution":[120],"crystal":[121],"structures":[122],"is":[123],"achieved;":[124],"detail":[126],"some":[127],"problems":[128],"potentials":[131],"were":[132,149],"discovered.":[133],"Charge-assisted":[134],"contacts":[135,148],"waters":[137],"appeared":[138],"as":[139],"exaggerated":[140],"AMBER,":[142],"stabilizing":[144],"contributions":[145],"water-to-methyl":[147],"underestimated.":[150]},"counts_by_year":[{"year":2026,"cited_by_count":2},{"year":2025,"cited_by_count":4},{"year":2024,"cited_by_count":4},{"year":2023,"cited_by_count":2},{"year":2022,"cited_by_count":2},{"year":2021,"cited_by_count":1},{"year":2020,"cited_by_count":4},{"year":2019,"cited_by_count":4},{"year":2018,"cited_by_count":8},{"year":2017,"cited_by_count":4},{"year":2016,"cited_by_count":3}],"updated_date":"2026-06-18T10:00:31.954636","created_date":"2025-10-10T00:00:00"}
