{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T07:27:36Z","timestamp":1745825256174,"version":"3.37.3"},"reference-count":96,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T00:00:00Z","timestamp":1707264000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T00:00:00Z","timestamp":1707264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100001409","name":"Department of Science and Technology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["DST\/NSM\/R&D_HPC_Applications\/2021\/03.18"],"award-info":[{"award-number":["DST\/NSM\/R&D_HPC_Applications\/2021\/03.18"]}],"id":[{"id":"10.13039\/501100001409","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Comput Aided Mol Des"],"published-print":{"date-parts":[[2024,12]]},"DOI":"10.1007\/s10822-023-00548-8","type":"journal-article","created":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T09:02:17Z","timestamp":1707296537000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Deciphering the molecular choreography of Janus kinase 2 inhibition via Gaussian accelerated molecular dynamics simulations: a dynamic odyssey"],"prefix":"10.1007","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4341-8370","authenticated-orcid":false,"given":"Md Fulbabu","family":"Sk","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8736-6253","authenticated-orcid":false,"given":"Sunanda","family":"Samanta","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7192-293X","authenticated-orcid":false,"given":"Sayan","family":"Poddar","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8451-9739","authenticated-orcid":false,"given":"Parimal","family":"Kar","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2024,2,7]]},"reference":[{"key":"548_CR1","first-page":"1347","volume":"7","author":"AG Harpur","year":"1992","unstructured":"Harpur AG, Andres AC, Ziemiecki A et al (1992) JAK2, a third member of the JAK family of protein tyrosine kinases. Oncogene 7:1347\u20131353","journal-title":"Oncogene"},{"key":"548_CR2","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1046\/j.1365-2443.1999.00263.x","volume":"4","author":"A Sasaki","year":"1999","unstructured":"Sasaki A, Yasukawa H, Suzuki A et al (1999) Cytokine-inducible SH2 protein-3 (CIS3\/SOCS3) inhibits Janus tyrosine kinase by binding through the N-terminal kinase inhibitory region as well as SH2 domain. Genes Cells 4:339\u2013351. https:\/\/doi.org\/10.1046\/j.1365-2443.1999.00263.x","journal-title":"Genes Cells"},{"issue":"Suppl","key":"548_CR3","doi-asserted-by":"publisher","first-page":"S121","DOI":"10.1016\/s0092-8674(02)00701-8","volume":"109","author":"JJ O\u2019Shea","year":"2002","unstructured":"O\u2019Shea JJ, Gadina M, Schreiber RD (2002) Cytokine signaling in 2002: new surprises in the Jak\/Stat pathway. Cell 109(Suppl):S121-131. https:\/\/doi.org\/10.1016\/s0092-8674(02)00701-8","journal-title":"Cell"},{"key":"548_CR4","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.jmb.2009.01.041","volume":"387","author":"NK Williams","year":"2009","unstructured":"Williams NK, Bamert RS, Patel O et al (2009) Dissecting Specificity in the Janus kinases: the structures of JAK-Specific inhibitors complexed to the JAK1 and JAK2 protein tyrosine kinase domains. J Mol Biol 387:219\u2013232. https:\/\/doi.org\/10.1016\/j.jmb.2009.01.041","journal-title":"J Mol Biol"},{"key":"548_CR5","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1002\/eji.201646680","volume":"47","author":"K Welsch","year":"2017","unstructured":"Welsch K, Holstein J, Laurence A, Ghoreschi K (2017) Targeting JAK\/STAT signalling in inflammatory skin diseases with small molecule inhibitors. Eur J Immunol 47:1096\u20131107. https:\/\/doi.org\/10.1002\/eji.201646680","journal-title":"Eur J Immunol"},{"key":"548_CR6","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1002\/jcph.1046","volume":"58","author":"C Banfield","year":"2018","unstructured":"Banfield C, Scaramozza M, Zhang W et al (2018) The safety, tolerability, pharmacokinetics, and pharmacodynamics of a TYK2\/JAK1 Inhibitor (PF-06700841) in healthy subjects and patients with plaque psoriasis. J Clin Pharmacol 58:434\u2013447. https:\/\/doi.org\/10.1002\/jcph.1046","journal-title":"J Clin Pharmacol"},{"key":"548_CR7","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.1242\/jcs.00963","volume":"117","author":"JS Rawlings","year":"2004","unstructured":"Rawlings JS, Rosler KM, Harrison DA (2004) The JAK\/STAT signaling pathway. J Cell Sci 117:1281\u20131283. https:\/\/doi.org\/10.1242\/jcs.00963","journal-title":"J Cell Sci"},{"key":"548_CR8","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1016\/j.immuni.2012.03.014","volume":"36","author":"JJ O\u2019Shea","year":"2012","unstructured":"O\u2019Shea JJ, Plenge R (2012) JAK and STAT signaling molecules in immunoregulation and immune-mediated disease. Immunity 36:542\u2013550. https:\/\/doi.org\/10.1016\/j.immuni.2012.03.014","journal-title":"Immunity"},{"key":"548_CR9","doi-asserted-by":"publisher","first-page":"20059","DOI":"10.1074\/jbc.R700016200","volume":"282","author":"C Schindler","year":"2007","unstructured":"Schindler C, Levy DE, Decker T (2007) JAK-STAT signaling: from interferons to cytokines. J Biol Chem 282:20059\u201320063. https:\/\/doi.org\/10.1074\/jbc.R700016200","journal-title":"J Biol Chem"},{"key":"548_CR10","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.clim.2016.09.014","volume":"189","author":"Z Yan","year":"2018","unstructured":"Yan Z, Gibson SA, Buckley JA et al (2018) Role of the JAK\/STAT signaling pathway in regulation of innate immunity in neuroinflammatory diseases. Clin Immunol 189:4\u201313. https:\/\/doi.org\/10.1016\/j.clim.2016.09.014","journal-title":"Clin Immunol"},{"key":"548_CR11","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1038\/nri1226","volume":"3","author":"K Shuai","year":"2003","unstructured":"Shuai K, Liu B (2003) Regulation of JAK-STAT signalling in the immune system. Nat Rev Immunol 3:900\u2013911. https:\/\/doi.org\/10.1038\/nri1226","journal-title":"Nat Rev Immunol"},{"key":"548_CR12","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1146\/annurev-med-051113-024537","volume":"66","author":"JJ O\u2019Shea","year":"2015","unstructured":"O\u2019Shea JJ, Schwartz DM, Villarino AV et al (2015) The JAK-STAT pathway: impact on human disease and therapeutic intervention. Annu Rev Med 66:311\u2013328. https:\/\/doi.org\/10.1146\/annurev-med-051113-024537","journal-title":"Annu Rev Med"},{"key":"548_CR13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1042\/BJ20140712","volume":"462","author":"JJ Babon","year":"2014","unstructured":"Babon JJ, Lucet IS, Murphy JM et al (2014) The molecular regulation of Janus kinase (JAK) activation. Biochem J 462:1\u201313. https:\/\/doi.org\/10.1042\/BJ20140712","journal-title":"Biochem J"},{"key":"548_CR14","doi-asserted-by":"publisher","first-page":"7195","DOI":"10.1021\/acs.jmedchem.5b00301","volume":"58","author":"LJ Farmer","year":"2015","unstructured":"Farmer LJ, Ledeboer MW, Hoock T et al (2015) Discovery of VX-509 (Decernotinib): a potent and selective Janus kinase 3 inhibitor for the treatment of autoimmune diseases. J Med Chem 58:7195\u20137216. https:\/\/doi.org\/10.1021\/acs.jmedchem.5b00301","journal-title":"J Med Chem"},{"key":"548_CR15","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1016\/j.phrs.2016.07.038","volume":"111","author":"R Roskoski","year":"2016","unstructured":"Roskoski R (2016) Janus kinase (JAK) inhibitors in the treatment of inflammatory and neoplastic diseases. Pharmacol Res 111:784\u2013803. https:\/\/doi.org\/10.1016\/j.phrs.2016.07.038","journal-title":"Pharmacol Res"},{"key":"548_CR16","doi-asserted-by":"publisher","first-page":"2517","DOI":"10.1098\/rstb.2012.0054","volume":"367","author":"SS Taylor","year":"2012","unstructured":"Taylor SS, Keshwani MM, Steichen JM, Kornev AP (2012) Evolution of the eukaryotic protein kinases as dynamic molecular switches. Philos Trans R Soc Lond B Biol Sci 367:2517\u20132528. https:\/\/doi.org\/10.1098\/rstb.2012.0054","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"548_CR17","doi-asserted-by":"publisher","first-page":"e1001680","DOI":"10.1371\/journal.pbio.1001680","volume":"11","author":"HS Meharena","year":"2013","unstructured":"Meharena HS, Chang P, Keshwani MM et al (2013) Deciphering the structural basis of eukaryotic protein kinase regulation. PLoS Biol 11:e1001680. https:\/\/doi.org\/10.1371\/journal.pbio.1001680","journal-title":"PLoS Biol"},{"key":"548_CR18","doi-asserted-by":"publisher","first-page":"4272","DOI":"10.1021\/bi036109b","volume":"43","author":"K Chatti","year":"2004","unstructured":"Chatti K, Farrar WL, Duh\u00e9 RJ (2004) Tyrosine phosphorylation of the Janus kinase 2 activation loop is essential for a high-activity catalytic state but dispensable for a Basal Catalytic State. Biochemistry 43:4272\u20134283. https:\/\/doi.org\/10.1021\/bi036109b","journal-title":"Biochemistry"},{"key":"548_CR19","doi-asserted-by":"publisher","first-page":"2497","DOI":"10.1128\/MCB.17.5.2497","volume":"17","author":"J Feng","year":"1997","unstructured":"Feng J, Witthuhn BA, Matsuda T et al (1997) Activation of Jak2 catalytic activity requires phosphorylation of Y1007 in the kinase activation loop. Mol Cell Biol 17:2497\u20132501. https:\/\/doi.org\/10.1128\/MCB.17.5.2497","journal-title":"Mol Cell Biol"},{"key":"548_CR20","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1021\/cb500696t","volume":"10","author":"PM-U Ung","year":"2015","unstructured":"Ung PM-U, Schlessinger A (2015) DFGmodel: predicting protein kinase structures in inactive states for structure-based discovery of type-II inhibitors. ACS Chem Biol 10:269\u2013278. https:\/\/doi.org\/10.1021\/cb500696t","journal-title":"ACS Chem Biol"},{"key":"548_CR21","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1016\/j.chembiol.2006.07.001","volume":"13","author":"C McInnes","year":"2006","unstructured":"McInnes C, Mezna M, Kontopidis G (2006) Catch the kinase conformer. Chem Biol 13:693\u2013694. https:\/\/doi.org\/10.1016\/j.chembiol.2006.07.001","journal-title":"Chem Biol"},{"key":"548_CR22","doi-asserted-by":"publisher","first-page":"14377","DOI":"10.1073\/pnas.0807988105","volume":"105","author":"AP Kornev","year":"2008","unstructured":"Kornev AP, Taylor SS, Eyck LFT (2008) A helix scaffold for the assembly of active protein kinases. Proc Natl Acad Sci USA 105:14377\u201314382. https:\/\/doi.org\/10.1073\/pnas.0807988105","journal-title":"Proc Natl Acad Sci USA"},{"key":"548_CR23","doi-asserted-by":"publisher","first-page":"9088","DOI":"10.1038\/s41598-017-09586-3","volume":"7","author":"X Kong","year":"2017","unstructured":"Kong X, Sun H, Pan P et al (2017) How does the L884P mutation confer resistance to Type-II inhibitors of JAK2 kinase: a comprehensive molecular modeling study. Sci Rep 7:9088. https:\/\/doi.org\/10.1038\/s41598-017-09586-3","journal-title":"Sci Rep"},{"key":"548_CR24","doi-asserted-by":"publisher","first-page":"45540","DOI":"10.1039\/C6RA06266K","volume":"6","author":"JJ Li","year":"2016","unstructured":"Li JJ, Tu J, Cheng P et al (2016) Insights into DFG-in and DFG-out JAK2 binding modes for a rational strategy of type II inhibitors combined computational study. RSC Adv 6:45540\u201345552. https:\/\/doi.org\/10.1039\/C6RA06266K","journal-title":"RSC Adv"},{"key":"548_CR25","doi-asserted-by":"publisher","first-page":"1230","DOI":"10.1021\/cb500129t","volume":"9","author":"Z Zhao","year":"2014","unstructured":"Zhao Z, Wu H, Wang L et al (2014) Exploration of type II binding mode: a privileged approach for kinase inhibitor focused drug discovery? ACS Chem Biol 9:1230\u20131241. https:\/\/doi.org\/10.1021\/cb500129t","journal-title":"ACS Chem Biol"},{"key":"548_CR26","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1038\/nchembio799","volume":"2","author":"Y Liu","year":"2006","unstructured":"Liu Y, Gray NS (2006) Rational design of inhibitors that bind to inactive kinase conformations. Nat Chem Biol 2:358\u2013364. https:\/\/doi.org\/10.1038\/nchembio799","journal-title":"Nat Chem Biol"},{"key":"548_CR27","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1093\/nar\/28.1.235","volume":"28","author":"HM Berman","year":"2000","unstructured":"Berman HM, Westbrook J, Feng Z et al (2000) The protein data bank. Nucleic Acids Res 28:235\u2013242. https:\/\/doi.org\/10.1093\/nar\/28.1.235","journal-title":"Nucleic Acids Res"},{"key":"548_CR28","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1158\/2159-8290.CD-11-0324","volume":"2","author":"R Andraos","year":"2012","unstructured":"Andraos R, Qian Z, Bonenfant D et al (2012) Modulation of activation-loop phosphorylation by JAK inhibitors is binding mode dependent. Cancer Discov 2:512\u2013523. https:\/\/doi.org\/10.1158\/2159-8290.CD-11-0324","journal-title":"Cancer Discov"},{"key":"548_CR29","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/bs.arcc.2017.06.005","volume":"13","author":"Y Miao","year":"2017","unstructured":"Miao Y, McCammon JA (2017) Gaussian accelerated molecular dynamics: theory, implementation, and applications. Annu Rep Comput Chem 13:231\u2013278. https:\/\/doi.org\/10.1016\/bs.arcc.2017.06.005","journal-title":"Annu Rep Comput Chem"},{"key":"548_CR30","doi-asserted-by":"publisher","first-page":"3584","DOI":"10.1021\/acs.jctc.5b00436","volume":"11","author":"Y Miao","year":"2015","unstructured":"Miao Y, Feher VA, McCammon JA (2015) Gaussian accelerated molecular dynamics: unconstrained enhanced sampling and free energy calculation. J Chem Theory Comput 11:3584\u20133595. https:\/\/doi.org\/10.1021\/acs.jctc.5b00436","journal-title":"J Chem Theory Comput"},{"key":"548_CR31","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1002\/prot.340110305","volume":"11","author":"T Ichiye","year":"1991","unstructured":"Ichiye T, Karplus M (1991) Collective motions in proteins: a covariance analysis of atomic fluctuations in molecular dynamics and normal mode simulations. Proteins 11:205\u2013217. https:\/\/doi.org\/10.1002\/prot.340110305","journal-title":"Proteins"},{"key":"548_CR32","doi-asserted-by":"publisher","first-page":"3314","DOI":"10.1021\/ct300418h","volume":"8","author":"BR Miller","year":"2012","unstructured":"Miller BR, McGee TD, Swails JM et al (2012) MMPBSA.py: an efficient program for end-state free energy calculations. J Chem Theory Comput 8:3314\u20133321. https:\/\/doi.org\/10.1021\/ct300418h","journal-title":"J Chem Theory Comput"},{"key":"548_CR33","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1021\/ar000033j","volume":"33","author":"PA Kollman","year":"2000","unstructured":"Kollman PA, Massova I, Reyes C et al (2000) Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum models. Acc Chem Res 33:889\u2013897. https:\/\/doi.org\/10.1021\/ar000033j","journal-title":"Acc Chem Res"},{"key":"548_CR34","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1002\/jcc.21372","volume":"31","author":"G Rastelli","year":"2010","unstructured":"Rastelli G, Del Rio A, Degliesposti G, Sgobba M (2010) Fast and accurate predictions of binding free energies using MM-PBSA and MM-GBSA. J Comput Chem 31:797\u2013810. https:\/\/doi.org\/10.1002\/jcc.21372","journal-title":"J Comput Chem"},{"key":"548_CR35","doi-asserted-by":"publisher","first-page":"3188","DOI":"10.1002\/jcc.21900","volume":"32","author":"B Xu","year":"2011","unstructured":"Xu B, Shen H, Zhu X, Li G (2011) Fast and accurate computation schemes for evaluating vibrational entropy of proteins. J Comput Chem 32:3188\u20133193. https:\/\/doi.org\/10.1002\/jcc.21900","journal-title":"J Comput Chem"},{"key":"548_CR36","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1007\/978-1-60327-058-8_8","volume":"426","author":"N Eswar","year":"2008","unstructured":"Eswar N, Eramian D, Webb B et al (2008) Protein structure modeling with MODELLER. Methods Mol Biol 426:145\u2013159. https:\/\/doi.org\/10.1007\/978-1-60327-058-8_8","journal-title":"Methods Mol Biol"},{"key":"548_CR37","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.1002\/jcc.20084","volume":"25","author":"EF Pettersen","year":"2004","unstructured":"Pettersen EF, Goddard TD, Huang CC et al (2004) UCSF Chimera-A visualization system for exploratory research and analysis. J Comput Chem 25:1605\u20131612. https:\/\/doi.org\/10.1002\/jcc.20084","journal-title":"J Comput Chem"},{"unstructured":"Maestro. Schr\u00f6dinger Release 2022-1: Schr\u00f6dinger 2021, LLC, New York","key":"548_CR38"},{"key":"548_CR39","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1021\/ct100578z","volume":"7","author":"MHM Olsson","year":"2011","unstructured":"Olsson MHM, S\u00f8ndergaard CR, Rostkowski M, Jensen JH (2011) PROPKA3: consistent treatment of internal and surface residues in empirical pKa predictions. J Chem Theory Comput 7:525\u2013537. https:\/\/doi.org\/10.1021\/ct100578z","journal-title":"J Chem Theory Comput"},{"key":"548_CR40","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1002\/wcms.1121","volume":"3","author":"R Salomon-Ferrer","year":"2013","unstructured":"Salomon-Ferrer R, Case DA, Walker RC (2013) An overview of the Amber biomolecular simulation package: Amber biomolecular simulation package. WIREs Comput Mol Sci 3:198\u2013210. https:\/\/doi.org\/10.1002\/wcms.1121","journal-title":"WIREs Comput Mol Sci"},{"key":"548_CR41","volume-title":"AMBER 2018","author":"DA Case","year":"2018","unstructured":"Case DA, Ben-Shalom IY, Brozell SR et al (2018) AMBER 2018. University of California, San Francisco"},{"key":"548_CR42","first-page":"U403","volume":"222","author":"J Wang","year":"2001","unstructured":"Wang J, Wang W, Kollman PA, David A (2001) Antechamber: an accessory software package for molecular mechanical calculations. J Am Chem Soc 222:U403","journal-title":"J Am Chem Soc"},{"key":"548_CR43","doi-asserted-by":"publisher","first-page":"3696","DOI":"10.1021\/acs.jctc.5b00255","volume":"11","author":"JA Maier","year":"2015","unstructured":"Maier JA, Martinez C, Kasavajhala K et al (2015) ff14SB: Improving the accuracy of protein side chain and backbone parameters from ff99SB. J Chem Theory Comput 11:3696\u20133713. https:\/\/doi.org\/10.1021\/acs.jctc.5b00255","journal-title":"J Chem Theory Comput"},{"key":"548_CR44","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1002\/jcc.20035","volume":"25","author":"J Wang","year":"2004","unstructured":"Wang J, Wolf RM, Caldwell JW et al (2004) Development and testing of a general amber force field. J Comput Chem 25:1157\u20131174. https:\/\/doi.org\/10.1002\/jcc.20035","journal-title":"J Comput Chem"},{"key":"548_CR45","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1007\/s00894-005-0028-4","volume":"12","author":"N Homeyer","year":"2006","unstructured":"Homeyer N, Horn AHC, Lanig H, Sticht H (2006) AMBER force-field parameters for phosphorylated amino acids in different protonation states: phosphoserine, phosphothreonine, phosphotyrosine, and phosphohistidine. J Mol Model 12:281\u2013289. https:\/\/doi.org\/10.1007\/s00894-005-0028-4","journal-title":"J Mol Model"},{"key":"548_CR46","doi-asserted-by":"publisher","first-page":"10096","DOI":"10.1063\/1.1808117","volume":"121","author":"DJ Price","year":"2004","unstructured":"Price DJ, Brooks CL (2004) A modified TIP3P water potential for simulation with Ewald summation. J Chem Phys 121:10096\u201310103. https:\/\/doi.org\/10.1063\/1.1808117","journal-title":"J Chem Phys"},{"key":"548_CR47","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1002\/bip.360320508","volume":"32","author":"RJ Loncharich","year":"1992","unstructured":"Loncharich RJ, Brooks BR, Pastor RW (1992) Langevin dynamics of peptides: the frictional dependence of isomerization rates of N-acetylalanyl-N\u2032-methylamide. Biopolymers 32:523\u2013535. https:\/\/doi.org\/10.1002\/bip.360320508","journal-title":"Biopolymers"},{"key":"548_CR48","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/0021-9991(77)90098-5","volume":"23","author":"J-P Ryckaert","year":"1977","unstructured":"Ryckaert J-P, Ciccotti G, Berendsen HJC (1977) Numerical integration of the cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes. J Comput Phys 23:327\u2013341. https:\/\/doi.org\/10.1016\/0021-9991(77)90098-5","journal-title":"J Comput Phys"},{"key":"548_CR49","doi-asserted-by":"publisher","first-page":"10089","DOI":"10.1063\/1.464397","volume":"98","author":"T Darden","year":"1993","unstructured":"Darden T, York D, Pedersen L (1993) Particle mesh Ewald: an N \u22c5log( N ) method for Ewald sums in large systems. J Chem Phys 98:10089\u201310092. https:\/\/doi.org\/10.1063\/1.464397","journal-title":"J Chem Phys"},{"key":"548_CR50","doi-asserted-by":"publisher","first-page":"3684","DOI":"10.1063\/1.448118","volume":"81","author":"HJC Berendsen","year":"1984","unstructured":"Berendsen HJC, Postma JPM, van Gunsteren WF et al (1984) Molecular dynamics with coupling to an external bath. J Chem Phys 81:3684\u20133690. https:\/\/doi.org\/10.1063\/1.448118","journal-title":"J Chem Phys"},{"key":"548_CR51","doi-asserted-by":"publisher","DOI":"10.1002\/wcms.1521","author":"J Wang","year":"2021","unstructured":"Wang J, Arantes PR, Bhattarai A et al (2021) Gaussian accelerated molecular dynamics: Principles and applications. WIREs Comput Mol Sci. https:\/\/doi.org\/10.1002\/wcms.1521","journal-title":"WIREs Comput Mol Sci"},{"key":"548_CR52","doi-asserted-by":"publisher","first-page":"2677","DOI":"10.1021\/ct500090q","volume":"10","author":"Y Miao","year":"2014","unstructured":"Miao Y, Sinko W, Pierce L et al (2014) Improved reweighting of accelerated molecular dynamics simulations for free energy calculation. J Chem Theory Comput 10:2677\u20132689. https:\/\/doi.org\/10.1021\/ct500090q","journal-title":"J Chem Theory Comput"},{"key":"548_CR53","doi-asserted-by":"publisher","first-page":"7343","DOI":"10.1039\/D0CP05733A","volume":"23","author":"N Amarnath Jonniya","year":"2021","unstructured":"Amarnath Jonniya N, Fulbabu Sk M, Kar P (2021) Characterizing an allosteric inhibitor-induced inactive state in with-no-lysine kinase 1 using Gaussian accelerated molecular dynamics simulations. Phys Chem Chem Phys 23:7343\u20137358. https:\/\/doi.org\/10.1039\/D0CP05733A","journal-title":"Phys Chem Chem Phys"},{"key":"548_CR54","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2020.1838327","author":"R Roy","year":"2020","unstructured":"Roy R, Mishra A, Poddar S et al (2020) Investigating the mechanism of recognition and structural dynamics of nucleoprotein-RNA complex from Peste des petits ruminants virus via Gaussian accelerated molecular dynamics simulations. J Biomol Struct Dyn. https:\/\/doi.org\/10.1080\/07391102.2020.1838327","journal-title":"J Biomol Struct Dyn"},{"key":"548_CR55","doi-asserted-by":"publisher","first-page":"6118","DOI":"10.1021\/acs.jcim.2c00961","volume":"62","author":"J Chen","year":"2022","unstructured":"Chen J, Zeng Q, Wang W et al (2022) Decoding the Identification mechanism of an SAM-III Riboswitch on ligands through Multiple Independent Gaussian-Accelerated Molecular Dynamics Simulations. J Chem Inf Model 62:6118\u20136132. https:\/\/doi.org\/10.1021\/acs.jcim.2c00961","journal-title":"J Chem Inf Model"},{"key":"548_CR56","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1080\/17460441.2018.1538207","volume":"13","author":"A Bhattarai","year":"2018","unstructured":"Bhattarai A, Miao Y (2018) Gaussian accelerated molecular dynamics for elucidation of drug pathways. Expert Opin Drug Discov 13:1055\u20131065. https:\/\/doi.org\/10.1080\/17460441.2018.1538207","journal-title":"Expert Opin Drug Discov"},{"key":"548_CR57","doi-asserted-by":"publisher","first-page":"1796","DOI":"10.1016\/j.bpj.2015.03.003","volume":"108","author":"Y Miao","year":"2015","unstructured":"Miao Y, Caliman AD, McCammon JA (2015) Allosteric effects of sodium ion binding on activation of the m3 muscarinic g-protein-coupled receptor. Biophys J 108:1796\u20131806. https:\/\/doi.org\/10.1016\/j.bpj.2015.03.003","journal-title":"Biophys J"},{"key":"548_CR58","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1007\/s10822-020-00355-5","volume":"34","author":"J Chen","year":"2020","unstructured":"Chen J, Wang W, Sun H et al (2020) Mutation-mediated influences on binding of anaplastic lymphoma kinase to crizotinib decoded by multiple replica Gaussian accelerated molecular dynamics. J Comput Aided Mol Des 34:1289\u20131305. https:\/\/doi.org\/10.1007\/s10822-020-00355-5","journal-title":"J Comput Aided Mol Des"},{"key":"548_CR59","doi-asserted-by":"publisher","first-page":"11129","DOI":"10.1073\/pnas.1807624115","volume":"115","author":"J Zhang","year":"2018","unstructured":"Zhang J, Wang N, Miao Y et al (2018) Identification of SLAC1 anion channel residues required for CO2\/bicarbonate sensing and regulation of stomatal movements. Proc Natl Acad Sci USA 115:11129\u201311137. https:\/\/doi.org\/10.1073\/pnas.1807624115","journal-title":"Proc Natl Acad Sci USA"},{"key":"548_CR60","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1080\/07391102.2017.1422025","volume":"37","author":"J-M Liao","year":"2019","unstructured":"Liao J-M, Wang Y-T (2019) In silico studies of conformational dynamics of Mu opioid receptor performed using gaussian accelerated molecular dynamics. J Biomol Struct Dyn 37:166\u2013177. https:\/\/doi.org\/10.1080\/07391102.2017.1422025","journal-title":"J Biomol Struct Dyn"},{"key":"548_CR61","doi-asserted-by":"publisher","first-page":"7828","DOI":"10.1038\/s41598-017-08224-2","volume":"7","author":"Y-T Wang","year":"2017","unstructured":"Wang Y-T, Chan Y-H (2017) Understanding the molecular basis of agonist\/antagonist mechanism of human mu opioid receptor through gaussian accelerated molecular dynamics method. Sci Rep 7:7828. https:\/\/doi.org\/10.1038\/s41598-017-08224-2","journal-title":"Sci Rep"},{"key":"548_CR62","doi-asserted-by":"publisher","first-page":"4283","DOI":"10.1038\/s41467-018-06680-6","volume":"9","author":"JB Park","year":"2018","unstructured":"Park JB, Kim YH, Yoo Y et al (2018) Structural basis for arginine glycosylation of host substrates by bacterial effector proteins. Nat Commun 9:4283. https:\/\/doi.org\/10.1038\/s41467-018-06680-6","journal-title":"Nat Commun"},{"key":"548_CR63","doi-asserted-by":"publisher","first-page":"1348","DOI":"10.1021\/jacs.9b10521","volume":"142","author":"KW East","year":"2020","unstructured":"East KW, Newton JC, Morzan UN et al (2020) Allosteric motions of the CRISPR-Cas9 HNH nuclease probed by NMR and molecular dynamics. J Am Chem Soc 142:1348\u20131358. https:\/\/doi.org\/10.1021\/jacs.9b10521","journal-title":"J Am Chem Soc"},{"key":"548_CR64","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1021\/acscentsci.9b00020","volume":"5","author":"CG Ricci","year":"2019","unstructured":"Ricci CG, Chen JS, Miao Y et al (2019) Deciphering off-target effects in CRISPR-Cas9 through accelerated molecular dynamics. ACS Cent Sci 5:651\u2013662. https:\/\/doi.org\/10.1021\/acscentsci.9b00020","journal-title":"ACS Cent Sci"},{"key":"548_CR65","doi-asserted-by":"publisher","first-page":"3084","DOI":"10.1021\/ct400341p","volume":"9","author":"DR Roe","year":"2013","unstructured":"Roe DR, Cheatham TE (2013) PTRAJ and CPPTRAJ: software for processing and analysis of molecular dynamics trajectory data. J Chem Theory Comput 9:3084\u20133095. https:\/\/doi.org\/10.1021\/ct400341p","journal-title":"J Chem Theory Comput"},{"key":"548_CR66","doi-asserted-by":"publisher","first-page":"1598","DOI":"10.1126\/science.1749933","volume":"254","author":"H Frauenfelder","year":"1991","unstructured":"Frauenfelder H, Sligar SG, Wolynes PG (1991) The energy landscapes and motions of proteins. Science 254:1598\u20131603. https:\/\/doi.org\/10.1126\/science.1749933","journal-title":"Science"},{"key":"548_CR67","doi-asserted-by":"publisher","first-page":"9970","DOI":"10.1073\/pnas.96.18.9970","volume":"96","author":"C-J Tsai","year":"1999","unstructured":"Tsai C-J, Ma B, Nussinov R (1999) Folding and binding cascades: shifts in energy landscapes. Proc Natl Acad Sci U S A 96:9970\u20139972. https:\/\/doi.org\/10.1073\/pnas.96.18.9970","journal-title":"Proc Natl Acad Sci U S A"},{"key":"548_CR68","doi-asserted-by":"publisher","first-page":"W94","DOI":"10.1093\/nar\/gkaa397","volume":"48","author":"A Felline","year":"2020","unstructured":"Felline A, Seeber M, Fanelli F (2020) webPSN v2.0: a webserver to infer fingerprints of structural communication in biomacromolecules. Nucleic Acids Res 48:W94\u2013W103. https:\/\/doi.org\/10.1093\/nar\/gkaa397","journal-title":"Nucleic Acids Res"},{"key":"548_CR69","doi-asserted-by":"publisher","first-page":"2436","DOI":"10.1002\/jcc.24467","volume":"37","author":"C Wang","year":"2016","unstructured":"Wang C, Nguyen PH, Pham K et al (2016) Calculating protein-ligand binding affinities with MMPBSA: method and error analysis. J Comput Chem 37:2436\u20132446. https:\/\/doi.org\/10.1002\/jcc.24467","journal-title":"J Comput Chem"},{"key":"548_CR70","doi-asserted-by":"publisher","first-page":"3224","DOI":"10.1021\/acs.jpcb.1c10733","volume":"126","author":"MF Sk","year":"2022","unstructured":"Sk MF, Jonniya NA, Roy R, Kar P (2022) Phosphorylation-induced conformational dynamics and inhibition of Janus Kinase 1 by suppressors of cytokine signaling 1. J Phys Chem B 126:3224\u20133239. https:\/\/doi.org\/10.1021\/acs.jpcb.1c10733","journal-title":"J Phys Chem B"},{"key":"548_CR71","doi-asserted-by":"publisher","first-page":"6195","DOI":"10.1021\/acsomega.1c06715","volume":"7","author":"MF Sk","year":"2022","unstructured":"Sk MF, Jonniya NA, Roy R, Kar P (2022) Unraveling the molecular mechanism of recognition of selected next-generation antirheumatoid arthritis inhibitors by Janus Kinase 1. ACS Omega 7:6195\u20136209. https:\/\/doi.org\/10.1021\/acsomega.1c06715","journal-title":"ACS Omega"},{"key":"548_CR72","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2020.590165","author":"MF Sk","year":"2020","unstructured":"Sk MF, Jonniya NA, Roy R et al (2020) Computational investigation of structural dynamics of SARS-CoV-2 methyltransferase-stimulatory factor heterodimer nsp16\/nsp10 bound to the cofactor SAM. Front Mol Biosci. https:\/\/doi.org\/10.3389\/fmolb.2020.590165","journal-title":"Front Mol Biosci"},{"key":"548_CR73","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1002\/prot.20033","volume":"55","author":"A Onufriev","year":"2004","unstructured":"Onufriev A, Bashford D, Case DA (2004) Exploring protein native states and large-scale conformational changes with a modified generalized born model. Proteins 55:383\u2013394. https:\/\/doi.org\/10.1002\/prot.20033","journal-title":"Proteins"},{"key":"548_CR74","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1016\/S0022-2836(03)00610-7","volume":"330","author":"H Gohlke","year":"2003","unstructured":"Gohlke H, Kiel C, Case DA (2003) Insights into protein-protein binding by binding free energy calculation and free energy decomposition for the Ras-Raf and Ras\u2013RalGDS complexes. J Mol Biol 330:891\u2013913. https:\/\/doi.org\/10.1016\/S0022-2836(03)00610-7","journal-title":"J Mol Biol"},{"key":"548_CR75","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.jmgm.2013.12.002","volume":"48","author":"S-F Chen","year":"2014","unstructured":"Chen S-F, Cao Y, Han S, Chen J-Z (2014) Insight into the structural mechanism for PKB\u03b1 allosteric inhibition by molecular dynamics simulations and free energy calculations. J Mol Graph Model 48:36\u201346. https:\/\/doi.org\/10.1016\/j.jmgm.2013.12.002","journal-title":"J Mol Graph Model"},{"key":"548_CR76","doi-asserted-by":"publisher","first-page":"5563","DOI":"10.1021\/acs.jctc.6b00600","volume":"12","author":"G La Sala","year":"2016","unstructured":"La Sala G, Riccardi L, Gaspari R et al (2016) HRD Motif as the central hub of the signaling network for activation loop autophosphorylation in Abl kinase. J Chem Theory Comput 12:5563\u20135574. https:\/\/doi.org\/10.1021\/acs.jctc.6b00600","journal-title":"J Chem Theory Comput"},{"key":"548_CR77","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2022.901603","author":"C Liu","year":"2022","unstructured":"Liu C, Li Z, Liu Z et al (2022) Understanding the P-loop conformation in the determination of inhibitor selectivity toward the Hepatocellular Carcinoma-Associated Dark Kinase STK17B. Front Mol Biosci. https:\/\/doi.org\/10.3389\/fmolb.2022.901603","journal-title":"Front Mol Biosci"},{"key":"548_CR78","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1007\/s10822-008-9214-7","volume":"22","author":"K Gohda","year":"2008","unstructured":"Gohda K, Hakoshima T (2008) A molecular mechanism of P-loop pliability of Rho-kinase investigated by molecular dynamic simulation. J Comput Aided Mol Des 22:789\u2013797. https:\/\/doi.org\/10.1007\/s10822-008-9214-7","journal-title":"J Comput Aided Mol Des"},{"key":"548_CR79","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1021\/ci200153c","volume":"51","author":"CRW Guimar\u00e3es","year":"2011","unstructured":"Guimar\u00e3es CRW, Rai BK, Munchhof MJ et al (2011) Understanding the Impact of the P-loop conformation on kinase selectivity. J Chem Inf Model 51:1199\u20131204. https:\/\/doi.org\/10.1021\/ci200153c","journal-title":"J Chem Inf Model"},{"key":"548_CR80","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1002\/pro.3556","volume":"28","author":"R Kalaivani","year":"2019","unstructured":"Kalaivani R, Narwani TJ, de Brevern AG, Srinivasan N (2019) Long-range molecular dynamics show that inactive forms of protein kinase A are more dynamic than active forms. Protein Sci 28:543\u2013560. https:\/\/doi.org\/10.1002\/pro.3556","journal-title":"Protein Sci"},{"key":"548_CR81","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.tibs.2010.09.006","volume":"36","author":"SS Taylor","year":"2011","unstructured":"Taylor SS, Kornev AP (2011) Protein kinases: evolution of dynamic regulatory proteins. Trends Biochem Sci 36:65\u201377. https:\/\/doi.org\/10.1016\/j.tibs.2010.09.006","journal-title":"Trends Biochem Sci"},{"key":"548_CR82","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1016\/j.jmb.2013.10.001","volume":"426","author":"Y Meng","year":"2014","unstructured":"Meng Y, Roux B (2014) Locking the active conformation of c-Src kinase through the phosphorylation of the activation loop. J Mol Biol 426:423\u2013435. https:\/\/doi.org\/10.1016\/j.jmb.2013.10.001","journal-title":"J Mol Biol"},{"key":"548_CR83","doi-asserted-by":"publisher","first-page":"808864","DOI":"10.3389\/fcell.2021.808864","volume":"9","author":"S Liang","year":"2021","unstructured":"Liang S, Wang Q, Qi X et al (2021) Deciphering the mechanism of gilteritinib overcoming lorlatinib resistance to the double mutant I1171N\/F1174I in anaplastic lymphoma kinase. Front Cell Dev Biol 9:808864. https:\/\/doi.org\/10.3389\/fcell.2021.808864","journal-title":"Front Cell Dev Biol"},{"key":"548_CR84","doi-asserted-by":"publisher","first-page":"862504","DOI":"10.3389\/fphar.2022.862504","volume":"13","author":"H Zhang","year":"2022","unstructured":"Zhang H, Zhu M, Li M et al (2022) Mechanistic insights into co-administration of allosteric and orthosteric drugs to overcome drug-resistance in T315I BCR-ABL1. Front Pharmacol 13:862504. https:\/\/doi.org\/10.3389\/fphar.2022.862504","journal-title":"Front Pharmacol"},{"key":"548_CR85","doi-asserted-by":"publisher","first-page":"747","DOI":"10.3390\/pharmaceutics13050747","volume":"13","author":"Y Qiu","year":"2021","unstructured":"Qiu Y, Yin X, Li X et al (2021) Untangling dual-targeting therapeutic mechanism of epidermal growth factor receptor (EGFR) based on reversed allosteric communication. Pharmaceutics 13:747. https:\/\/doi.org\/10.3390\/pharmaceutics13050747","journal-title":"Pharmaceutics"},{"key":"548_CR86","doi-asserted-by":"publisher","first-page":"567","DOI":"10.3390\/biom11040567","volume":"11","author":"Z Musavizadeh","year":"2021","unstructured":"Musavizadeh Z, Grottesi A, Guarguaglini G, Paiardini A (2021) Phosphorylation, Mg-ADP, and inhibitors differentially shape the conformational dynamics of the A-Loop of Aurora-A. Biomolecules 11:567. https:\/\/doi.org\/10.3390\/biom11040567","journal-title":"Biomolecules"},{"key":"548_CR87","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1021\/jm501603h","volume":"58","author":"RSK Vijayan","year":"2015","unstructured":"Vijayan RSK, He PP, Modi V et al (2015) Conformational analysis of the DFG-out kinase motif and biochemical profiling of structurally validated type II inhibitors. J Med Chem 58:466\u2013479. https:\/\/doi.org\/10.1021\/jm501603h","journal-title":"J Med Chem"},{"key":"548_CR88","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1016\/j.molcel.2004.08.024","volume":"15","author":"B Nolen","year":"2004","unstructured":"Nolen B, Taylor S, Ghosh G (2004) Regulation of protein kinases; controlling activity through activation segment conformation. Mol Cell 15:661\u2013675. https:\/\/doi.org\/10.1016\/j.molcel.2004.08.024","journal-title":"Mol Cell"},{"key":"548_CR89","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1073\/pnas.1207104110","volume":"110","author":"K Oruganty","year":"2013","unstructured":"Oruganty K, Talathi NS, Wood ZA, Kannan N (2013) Identification of a hidden strain switch provides clues to an ancient structural mechanism in protein kinases. Proc Natl Acad Sci U S A 110:924\u2013929. https:\/\/doi.org\/10.1073\/pnas.1207104110","journal-title":"Proc Natl Acad Sci U S A"},{"key":"548_CR90","doi-asserted-by":"publisher","first-page":"6818","DOI":"10.1073\/pnas.1814279116","volume":"116","author":"V Modi","year":"2019","unstructured":"Modi V, Dunbrack RL (2019) Defining a new nomenclature for the structures of active and inactive kinases. Proc Natl Acad Sci U S A 116:6818\u20136827. https:\/\/doi.org\/10.1073\/pnas.1814279116","journal-title":"Proc Natl Acad Sci U S A"},{"key":"548_CR91","doi-asserted-by":"publisher","first-page":"15092","DOI":"10.1021\/jacs.9b06064","volume":"141","author":"C-C Tsai","year":"2019","unstructured":"Tsai C-C, Yue Z, Shen J (2019) How electrostatic coupling enables conformational plasticity in a tyrosine kinase. J Am Chem Soc 141:15092\u201315101. https:\/\/doi.org\/10.1021\/jacs.9b06064","journal-title":"J Am Chem Soc"},{"doi-asserted-by":"publisher","unstructured":"M\u00f6bitz H (2015) The ABC of protein kinase conformations. Biochim Biophys Acta (BBA)\u2014Proteins Proteom 1854: 1555\u20131566. https:\/\/doi.org\/10.1016\/j.bbapap.2015.03.009","key":"548_CR92","DOI":"10.1016\/j.bbapap.2015.03.009"},{"key":"548_CR93","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1038\/s41557-018-0077-9","volume":"10","author":"MM Sultan","year":"2018","unstructured":"Sultan MM, Kiss G, Pande VS (2018) Towards simple kinetic models of functional dynamics for a kinase subfamily. Nature Chem 10:903\u2013909. https:\/\/doi.org\/10.1038\/s41557-018-0077-9","journal-title":"Nature Chem"},{"key":"548_CR94","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1182\/blood-2005-06-2413","volume":"107","author":"IS Lucet","year":"2006","unstructured":"Lucet IS, Fantino E, Styles M et al (2006) The structural basis of Janus kinase 2 inhibition by a potent and specific pan-Janus kinase inhibitor. Blood 107:176\u2013183. https:\/\/doi.org\/10.1182\/blood-2005-06-2413","journal-title":"Blood"},{"key":"548_CR95","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1021\/acsomega.9b02800","volume":"5","author":"K Sanachai","year":"2020","unstructured":"Sanachai K, Mahalapbutr P, Choowongkomon K et al (2020) Insights into the binding recognition and susceptibility of Tofacitinib toward Janus Kinases. ACS Omega 5:369\u2013377. https:\/\/doi.org\/10.1021\/acsomega.9b02800","journal-title":"ACS Omega"},{"key":"548_CR96","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1016\/j.chembiol.2023.05.007","volume":"30","author":"ML Arwood","year":"2023","unstructured":"Arwood ML, Liu Y, Harkins SK et al (2023) New scaffolds for type II JAK2 inhibitors overcome the acquired G993A resistance mutation. Cell Chem Biol 30:618-631.e12. https:\/\/doi.org\/10.1016\/j.chembiol.2023.05.007","journal-title":"Cell Chem Biol"}],"container-title":["Journal of Computer-Aided Molecular Design"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10822-023-00548-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10822-023-00548-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10822-023-00548-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T12:15:07Z","timestamp":1732623307000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10822-023-00548-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,7]]},"references-count":96,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["548"],"URL":"https:\/\/doi.org\/10.1007\/s10822-023-00548-8","relation":{},"ISSN":["0920-654X","1573-4951"],"issn-type":[{"type":"print","value":"0920-654X"},{"type":"electronic","value":"1573-4951"}],"subject":[],"published":{"date-parts":[[2024,2,7]]},"assertion":[{"value":"5 October 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 December 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 February 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"There is no human or animal experiment in this study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"8"}}