{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T04:03:53Z","timestamp":1789531433234,"version":"build-2803163510"},"reference-count":84,"publisher":"American Chemical Society (ACS)","issue":"11","license":[{"start":{"date-parts":[[2020,10,22]],"date-time":"2020-10-22T00:00:00Z","timestamp":1603324800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Chem. Theory Comput."],"published-print":{"date-parts":[[2020,11,10]]},"DOI":"10.1021\/acs.jctc.0c00634","type":"journal-article","created":{"date-parts":[[2020,10,22]],"date-time":"2020-10-22T17:13:06Z","timestamp":1603386786000},"page":"7160-7172","source":"Crossref","is-referenced-by-count":34,"title":["Virtual Double-System Single-Box: A Nonequilibrium Alchemical Technique for Absolute Binding Free Energy Calculations: Application to Ligands of the SARS-CoV-2 Main Protease"],"prefix":"10.1021","volume":"16","author":[{"given":"Marina","family":"Macchiagodena","sequence":"first","affiliation":[{"name":"Dipartimento di Chimica \u201cUgo Schiff\u201d, Universit\u00e0 degli Studi di Firenze, Via della Lastruccia 3, 50019 Sesto Fiorentino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0240-161X","authenticated-orcid":true,"given":"Marco","family":"Pagliai","sequence":"additional","affiliation":[{"name":"Dipartimento di Chimica \u201cUgo Schiff\u201d, Universit\u00e0 degli Studi di Firenze, Via della Lastruccia 3, 50019 Sesto Fiorentino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurice","family":"Karrenbrock","sequence":"additional","affiliation":[{"name":"Dipartimento di Chimica \u201cUgo Schiff\u201d, Universit\u00e0 degli Studi di Firenze, Via della Lastruccia 3, 50019 Sesto Fiorentino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Guarnieri","sequence":"additional","affiliation":[{"name":"ENEA, Portici Research Centre, DTE-ICT-HPC P.le E. Fermi, 1, I-80055 Portici (NA), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Iannone","sequence":"additional","affiliation":[{"name":"ENEA, Portici Research Centre, DTE-ICT-HPC P.le E. Fermi, 1, I-80055 Portici (NA), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2667-3847","authenticated-orcid":true,"given":"Piero","family":"Procacci","sequence":"additional","affiliation":[{"name":"Dipartimento di Chimica \u201cUgo Schiff\u201d, Universit\u00e0 degli Studi di Firenze, Via della Lastruccia 3, 50019 Sesto Fiorentino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,10,22]]},"reference":[{"key":"ref1\/cit1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2223-y"},{"key":"ref2\/cit2","doi-asserted-by":"crossref","unstructured":"Osipiuk, J.; Jedrzejczak, R.; Tesar, C.; Endres, M.; Stols, L.; Babnigg, G.; Kim, Y.; Michalska, K.; Joachimiak, A. The Crystal Structure of Papain-Like Protease of SARS CoV-2, RSCB PDB, 2020; pdbode: 6W9C, 2020.","DOI":"10.2210\/pdb6w9c\/pdb"},{"key":"ref3\/cit3","doi-asserted-by":"publisher","DOI":"10.1038\/s41557-020-0496-2"},{"key":"ref4\/cit4","doi-asserted-by":"publisher","DOI":"10.1111\/febs.12936"},{"key":"ref5\/cit5","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb3405"},{"key":"ref6\/cit6","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2012-7"},{"key":"ref7\/cit7","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1835675100"},{"key":"ref8\/cit8","doi-asserted-by":"crossref","unstructured":"Liu, X.; Zhang, B.; Jin, Z.; Yang, H.; Rao, Z. The Crystal Structure of 2019-nCoV Main Protease in Complex with an Inhibitor N3, SCB PDB, 2020; pdbode: 6LU7, 2020.","DOI":"10.2210\/pdb7bqy\/pdb"},{"key":"ref9\/cit9","doi-asserted-by":"publisher","DOI":"10.1016\/j.cplett.2020.137489"},{"key":"ref10\/cit10","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b01461"},{"key":"ref11\/cit11","first-page":"1330","volume":"12","author":"Johansson M. H.","year":"2012","journal-title":"Mini-Rev. Med. Chem."},{"key":"ref12\/cit12","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2008.08.082"},{"key":"ref13\/cit13","first-page":"1","volume-title":"Progress in Medicinal Chemistry","volume":"58","author":"Vasudevan A.","year":"2019"},{"key":"ref14\/cit14","volume-title":"Probe Reports from the NIH Molecular Libraries Program","author":"Jacobs J.","year":"2010"},{"key":"ref15\/cit15","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1021\/jm301580n","volume":"56","author":"Jacobs J.","year":"2013","journal-title":"J. Med. Chem."},{"key":"ref16\/cit16","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2286-9"},{"key":"ref17\/cit17","unstructured":"COVID Moonshot. https:\/\/postera.ai\/covid (accessed June 18, 2020)."},{"key":"ref18\/cit18","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.9b00634"},{"key":"ref19\/cit19","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21256"},{"key":"ref20\/cit20","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jctc.8b00305"},{"key":"ref21\/cit21","doi-asserted-by":"publisher","DOI":"10.1063\/1.1740409"},{"key":"ref22\/cit22","doi-asserted-by":"publisher","DOI":"10.1063\/1.1749657"},{"key":"ref23\/cit23","doi-asserted-by":"publisher","DOI":"10.1021\/jp102971x"},{"key":"ref24\/cit24","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmgm.2016.11.018"},{"key":"ref25\/cit25","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.0c00491"},{"key":"ref26\/cit26","doi-asserted-by":"publisher","DOI":"10.1021\/ja512751q"},{"key":"ref27\/cit27","doi-asserted-by":"publisher","DOI":"10.1063\/1.5123154"},{"key":"ref28\/cit28","doi-asserted-by":"publisher","DOI":"10.1039\/D0CC03558K"},{"key":"ref29\/cit29","doi-asserted-by":"publisher","DOI":"10.1021\/ct500142c"},{"key":"ref30\/cit30","doi-asserted-by":"publisher","DOI":"10.1021\/ct500964e"},{"key":"ref31\/cit31","doi-asserted-by":"publisher","DOI":"10.1039\/C5CP05519A"},{"key":"ref32\/cit32","doi-asserted-by":"publisher","DOI":"10.1039\/C5CP05521K"},{"key":"ref33\/cit33","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1002\/jcc.21388","volume":"31","author":"Marsili S.","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref34\/cit34","doi-asserted-by":"publisher","DOI":"10.1021\/jp807701h"},{"key":"ref35\/cit35","doi-asserted-by":"publisher","DOI":"10.1101\/2020.04.15.043240"},{"key":"ref36\/cit36","doi-asserted-by":"publisher","DOI":"10.1007\/s10822-018-0170-6"},{"key":"ref37\/cit37","doi-asserted-by":"publisher","DOI":"10.1101\/795005"},{"key":"ref38\/cit38","doi-asserted-by":"publisher","DOI":"10.1007\/s10822-020-00290-5"},{"key":"ref39\/cit39","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/978-1-4939-1465-4_9","volume-title":"Molecular Modeling of Protein","author":"Gapsys V.","year":"2015"},{"key":"ref40\/cit40","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jctc.8b00280"},{"key":"ref41\/cit41","doi-asserted-by":"publisher","DOI":"10.1063\/1.449208"},{"key":"ref42\/cit42","doi-asserted-by":"publisher","DOI":"10.1126\/science.2727695"},{"key":"ref43\/cit43","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jctc.6b01192"},{"key":"ref44\/cit44","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(97)78756-3"},{"key":"ref45\/cit45","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevLett.78.2690"},{"key":"ref46\/cit46","doi-asserted-by":"publisher","DOI":"10.1063\/1.2360273"},{"key":"ref47\/cit47","doi-asserted-by":"publisher","DOI":"10.1023\/A:1023208217925"},{"key":"ref48\/cit48","doi-asserted-by":"publisher","DOI":"10.1063\/1.5120615"},{"key":"ref49\/cit49","doi-asserted-by":"publisher","DOI":"10.1063\/1.5120616"},{"key":"ref50\/cit50","doi-asserted-by":"publisher","DOI":"10.1063\/1.4918558"},{"key":"ref51\/cit51","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9991(76)90078-4"},{"key":"ref52\/cit52","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevLett.91.140601"},{"key":"ref53\/cit53","doi-asserted-by":"publisher","DOI":"10.1063\/1.470117"},{"key":"ref54\/cit54","doi-asserted-by":"publisher","DOI":"10.1063\/1.477788"},{"key":"ref55\/cit55","doi-asserted-by":"publisher","DOI":"10.1007\/s10822-018-0151-9"},{"key":"ref56\/cit56","doi-asserted-by":"publisher","DOI":"10.1007\/s10822-019-00233-9"},{"key":"ref57\/cit57","doi-asserted-by":"publisher","DOI":"10.1007\/s10822-020-00312-2"},{"key":"ref58\/cit58","doi-asserted-by":"publisher","DOI":"10.1021\/bi061746y"},{"key":"ref59\/cit59","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1049"},{"key":"ref60\/cit60","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2020.1753577"},{"key":"ref61\/cit61","doi-asserted-by":"publisher","DOI":"10.1021\/ci049714+"},{"key":"ref62\/cit62","doi-asserted-by":"publisher","DOI":"10.1186\/1758-2946-3-33"},{"key":"ref63\/cit63","doi-asserted-by":"publisher","DOI":"10.1063\/1.445869"},{"key":"ref64\/cit64","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.6b00151"},{"key":"ref65\/cit65","doi-asserted-by":"publisher","DOI":"10.1039\/C9CP02808K"},{"key":"ref66\/cit66","doi-asserted-by":"publisher","DOI":"10.1101\/2020.04.15.043240"},{"key":"ref67\/cit67","doi-asserted-by":"publisher","DOI":"10.1109\/HPCS48598.2019.9188135"},{"key":"ref68\/cit68","doi-asserted-by":"publisher","DOI":"10.1002\/prot.22711"},{"key":"ref69\/cit69","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.7b00145"},{"key":"ref70\/cit70","doi-asserted-by":"publisher","DOI":"10.1063\/1.477136"},{"key":"ref71\/cit71","doi-asserted-by":"publisher","DOI":"10.1063\/1.463137"},{"key":"ref72\/cit72","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-987X(19971130)18:15<1848::AID-JCC2>3.0.CO;2-O"},{"key":"ref73\/cit73","doi-asserted-by":"publisher","DOI":"10.1021\/ct100281c"},{"key":"ref74\/cit74","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1954.10501232"},{"key":"ref75\/cit75","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1635159100"},{"key":"ref76\/cit76","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.2517-6161.1977.tb01600.x","volume":"39","author":"Dempster A.","year":"1977","journal-title":"J. R. Stat. Soc., B"},{"key":"ref77\/cit77","doi-asserted-by":"publisher","DOI":"10.1561\/2000000034"},{"key":"ref78\/cit78","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(01)94977-9"},{"key":"ref79\/cit79","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/8.2.127"},{"key":"ref80\/cit80","doi-asserted-by":"publisher","DOI":"10.1016\/0263-7855(96)00018-5"},{"key":"ref81\/cit81","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt055"},{"key":"ref82\/cit82","unstructured":"Case, D.; Belfon, K.; Ben-Shalom, I.; Brozell, S.; Cerutti, D.; Cheatham, T.; Cruzeiro, V.; Darden, T.; Duke, R.; Giambasu, G.; Gilson, M.; Gohlke, H.; Goetz, A.; Harris, R.; Izadi, S.; Izmailov, S.; Kasavajhala, K.; Kovalenko, A.; Krasny, R.; Kurtzman, T.; Lee, T.; LeGrand, S.; Li, P.; Lin, C.; Liu, J.; Luchko, T.; Luo, R.; Man, V.; Merz, K.; Miao, Y.; Mikhailovskii, O.; Monard, G.; Nguyen, H.; Onufriev, A.; Pan, F.; Pantano, S.; Qi, R.; Roe, D.; Roitberg, A.; Sagui, C.; Schott-Verdugo, S.; Shen, J.; Simmerling, C.; Skrynnikov, N. R.; Smith, J.; Swails, J.; Walker, R.; Wang, J.; Wilson, L.; Wolf, R.; Wu, X.; Xiong, Y.; Xue, Y.; York, D.; Kollman, P.\n                      AMBER\n                      ; University of California: San Francisco, 2020."},{"key":"ref83\/cit83","doi-asserted-by":"publisher","DOI":"10.1021\/ct060037v"},{"key":"ref84\/cit84","unstructured":"HREM Trajectories for the Target State of the Ligands Reported in Table 3 can be Downloaded from the Institutional Site of the Florence University, 2020. https:\/\/drive.google.com\/drive\/folders\/1hsOhJHQoJAaP3RgmW3XbfvZNa04s-Era?usp=sharing."}],"container-title":["Journal of Chemical Theory and Computation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jctc.0c00634","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jctc.0c00634","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T04:44:06Z","timestamp":1723783446000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/doi\/10.1021\/acs.jctc.0c00634"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,22]]},"references-count":84,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2020,11,10]]}},"alternative-id":["10.1021\/acs.jctc.0c00634"],"URL":"https:\/\/doi.org\/10.1021\/acs.jctc.0c00634","relation":{},"ISSN":["1549-9618","1549-9626"],"issn-type":[{"value":"1549-9618","type":"print"},{"value":"1549-9626","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,22]]}}}