{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T05:40:46Z","timestamp":1781502046706,"version":"3.54.1"},"reference-count":57,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,2,6]],"date-time":"2022-02-06T00:00:00Z","timestamp":1644105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["18-74-10056"],"award-info":[{"award-number":["18-74-10056"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Lomonosov Moscow State University state task","award":["\u0410\u0410\u0410\u0410-\u041021- 121011290089-4"],"award-info":[{"award-number":["\u0410\u0410\u0410\u0410-\u041021- 121011290089-4"]}]},{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["075-15-2019- 1671"],"award-info":[{"award-number":["075-15-2019- 1671"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The increasing antibiotic resistance is a clinical problem worldwide. Numerous Gram-negative bacteria have already become resistant to the most widely used class of antibacterial drugs, \u03b2-lactams. One of the main mechanisms is inactivation of \u03b2-lactam antibiotics by bacterial \u03b2-lactamases. Appearance and spread of these enzymes represent a continuous challenge for the clinical treatment of infections and for the design of new antibiotics and inhibitors. Drug repurposing is a prospective approach for finding new targets for drugs already approved for use. We describe here the inhibitory potency of known detoxifying antidote 2,3-dimercaptopropane-1-sulfonate (unithiol) against metallo-\u03b2-lactamases. Unithiol acts as a competitive inhibitor of meropenem hydrolysis by recombinant metallo-\u03b2-lactamase NDM-1 with the KI of 16.7 \u00b5M. It is an order of magnitude lower than the KI for l-captopril, the inhibitor of angiotensin-converting enzyme approved as a drug for the treatment of hypertension. Phenotypic methods demonstrate that the unithiol inhibits natural metallo-\u03b2-lactamases NDM-1 and VIM-2 produced by carbapenem-resistant K. pneumoniae and P. aeruginosa bacterial strains. The 3D full atom structures of unithiol complexes with NDM-1 and VIM-2 are obtained using QM\/MM modeling. The thiol group is located between zinc cations of the active site occupying the same place as the catalytic hydroxide anion in the enzyme\u2013substrate complex. The sulfate group forms both a coordination bond with a zinc cation and hydrogen bonds with the positively charged residue, lysine or arginine, responsible for proper orientation of antibiotics upon binding to the active site prior to hydrolysis. Thus, we demonstrate both experimentally and theoretically that the unithiol is a prospective competitive inhibitor of metallo-\u03b2-lactamases and it can be utilized in complex therapy together with the known \u03b2-lactam antibiotics.<\/jats:p>","DOI":"10.3390\/ijms23031834","type":"journal-article","created":{"date-parts":[[2022,2,6]],"date-time":"2022-02-06T20:36:47Z","timestamp":1644179807000},"page":"1834","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Drug Repurposing of the Unithiol: Inhibition of Metallo-\u03b2-Lactamases for the Treatment of Carbapenem-Resistant Gram-Negative Bacterial Infections"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0352-4902","authenticated-orcid":false,"given":"Vitaly G.","family":"Grigorenko","sequence":"first","affiliation":[{"name":"Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7117-3089","authenticated-orcid":false,"given":"Maria G.","family":"Khrenova","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia"},{"name":"Bach Institute of Biochemistry, Federal Research Centre \u201cFundamentals of Biotechnology\u201d of the Russian Academy of Sciences, 119071 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina P.","family":"Andreeva","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4025-5967","authenticated-orcid":false,"given":"Maya Yu.","family":"Rubtsova","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia I.","family":"Lev","sequence":"additional","affiliation":[{"name":"State Research Center for Applied Microbiology & Biotechnology, 142279 Obolensk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana S.","family":"Novikova","sequence":"additional","affiliation":[{"name":"State Research Center for Applied Microbiology & Biotechnology, 142279 Obolensk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena V.","family":"Detusheva","sequence":"additional","affiliation":[{"name":"State Research Center for Applied Microbiology & Biotechnology, 142279 Obolensk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6053-2621","authenticated-orcid":false,"given":"Nadezhda K.","family":"Fursova","sequence":"additional","affiliation":[{"name":"State Research Center for Applied Microbiology & Biotechnology, 142279 Obolensk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan A.","family":"Dyatlov","sequence":"additional","affiliation":[{"name":"State Research Center for Applied Microbiology & Biotechnology, 142279 Obolensk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey M.","family":"Egorov","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Eichenberger, E.M., and Thaden, J.T. (2019). Epidemiology and Mechanisms of Resistance of Extensively Drug Resistant Gram-Negative Bacteria. Antibiotics, 8.","DOI":"10.3390\/antibiotics8020037"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"36","DOI":"10.4103\/jgid.jgid_110_18","article-title":"Global contributors to antibiotic resistance","volume":"11","author":"Chokshi","year":"2019","journal-title":"J. Glob. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"539","DOI":"10.3389\/fmicb.2019.00539","article-title":"Emerging Strategies to Combat ESKAPE Pathogens in the Era of Antimicrobial Resistance: A Review","volume":"10","author":"Mulani","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1111\/eva.12235","article-title":"Public health evolutionary biology of antimicrobial resistance: Priorities for intervention","volume":"8","author":"Baquero","year":"2015","journal-title":"Evol. Appl."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2893","DOI":"10.1016\/j.envpol.2009.05.051","article-title":"Environmental pollution by antibiotics and by antibiotic resistance determinants","volume":"157","author":"Martinez","year":"2009","journal-title":"Environ. Pollut."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e00088-17","DOI":"10.1128\/CMR.00088-17","article-title":"Mobile Genetic Elements Associated with Antimicrobial Resistance","volume":"31","author":"Partridge","year":"2018","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1093\/jac\/dkx488","article-title":"Plasmids carrying antimicrobial resistance genes in Enterobacteriaceae","volume":"73","author":"Rozwandowicz","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1021\/cr030102i","article-title":"Bacterial Resistance to \u03b2-Lactam Antibiotics: Compelling Opportunism, Compelling Opportunity","volume":"105","author":"Fisher","year":"2005","journal-title":"Chem. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"112829","DOI":"10.1016\/j.ejmech.2020.112829","article-title":"\u03b2-lactam antibiotics: An overview from a medicinal chemistry perspective","volume":"208","author":"Lima","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"a025239","DOI":"10.1101\/cshperspect.a025239","article-title":"\u03b2-Lactamases: A Focus on Current Challenges","volume":"7","author":"Bonomo","year":"2017","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e01076-18","DOI":"10.1128\/AAC.01076-18","article-title":"Past and Present Perspectives on \u03b2-Lactamases","volume":"62","author":"Bush","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3472","DOI":"10.1016\/j.jmb.2019.04.002","article-title":"\u03b2-Lactamases and \u03b2-Lactamase Inhibitors in the 21st Century","volume":"431","author":"Tooke","year":"2019","journal-title":"J. Mol. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/s41579-019-0159-8","article-title":"Interplay between \u03b2-lactamases and new \u03b2-lactamase inhibitors","volume":"17","author":"Bush","year":"2019","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1128\/AAC.01009-09","article-title":"Updated Functional Classification of -Lactamases","volume":"54","author":"Bush","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1111\/j.1749-6632.2012.06796.x","article-title":"Metallo-\u03b2-lactamase structure and function","volume":"1277","author":"Palzkill","year":"2013","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.mib.2017.10.026","article-title":"Inhibitors of metallo-\u03b2-lactamases","volume":"39","author":"Rotondo","year":"2017","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.tips.2018.03.007","article-title":"The Continuing Challenge of Metallo-\u03b2-Lactamase Inhibition: Mechanism Matters","volume":"39","author":"Ju","year":"2018","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/249856","article-title":"Worldwide Dissemination of the NDM-Type Carbapenemases in Gram-Negative Bacteria","volume":"2014","author":"Dortet","year":"2014","journal-title":"Biomed Res. Int."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.2174\/1389450116666151001105622","article-title":"B1-Metallo-\u03b2-Lactamases: Where Do We Stand?","volume":"17","author":"Mojica","year":"2016","journal-title":"Curr. Drug Targets"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Krivitskaya, A.V., and Khrenova, M.G. (2021). Boronic Acids as Prospective Inhibitors of Metallo-\u03b2-Lactamases: Efficient Chemical Reaction in the Enzymatic Active Site Revealed by Molecular Modeling. Molecules, 26.","DOI":"10.3390\/molecules26072026"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Liang, Z., Li, L., Wang, Y., Chen, L., Kong, X., Hong, Y., Lan, L., Zheng, M., Guang-Yang, C., and Liu, H. (2011). Molecular Basis of NDM-1, a New Antibiotic Resistance Determinant. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023606"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2242","DOI":"10.1038\/s41467-017-02339-w","article-title":"The mechanism of NDM-1-catalyzed carbapenem hydrolysis is distinct from that of penicillin or cephalosporin hydrolysis","volume":"8","author":"Feng","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"14694","DOI":"10.1021\/ja508388e","article-title":"Structural and Mechanistic Insights into NDM-1 Catalyzed Hydrolysis of Cephalosporins","volume":"136","author":"Feng","year":"2014","journal-title":"J. Am. Chem. Soc."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Liu, Y., Li, R., Xiao, X., and Wang, Z. (2018). Molecules that Inhibit Bacterial Resistance Enzymes. Molecules, 24.","DOI":"10.3390\/molecules24010043"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7491","DOI":"10.1021\/acs.jmedchem.9b01976","article-title":"Discovery of Cyclic Boronic Acid QPX7728, an Ultrabroad-Spectrum Inhibitor of Serine and Metallo-\u03b2-lactamases","volume":"63","author":"Hecker","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/j.ejmech.2019.06.092","article-title":"Boron in drug design: Recent advances in the development of new therapeutic agents","volume":"179","author":"Fernandes","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2789","DOI":"10.1021\/acs.jmedchem.9b01518","article-title":"Discovery of Taniborbactam (VNRX-5133): A Broad-Spectrum Serine- and Metallo-\u03b2-lactamase Inhibitor for Carbapenem-Resistant Bacterial Infections","volume":"63","author":"Liu","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1021\/acsinfecdis.8b00247","article-title":"Ten Years with New Delhi Metallo-\u03b2-lactamase-1 (NDM-1): From Structural Insights to Inhibitor Design","volume":"5","author":"Linciano","year":"2019","journal-title":"ACS Infect. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/nature13445","article-title":"Aspergillomarasmine A overcomes metallo-\u03b2-lactamase antibiotic resistance","volume":"510","author":"King","year":"2014","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1880","DOI":"10.1021\/acs.biochem.7b01299","article-title":"Structural and Kinetic Studies of the Potent Inhibition of Metallo-\u03b2-lactamases by 6-Phosphonomethylpyridine-2-carboxylates","volume":"57","author":"Hinchliffe","year":"2018","journal-title":"Biochemistry"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"E3745","DOI":"10.1073\/pnas.1601368113","article-title":"Cross-class metallo-\u03b2-lactamase inhibition by bisthiazolidines reveals multiple binding modes","volume":"113","author":"Hinchliffe","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/nrd.2018.168","article-title":"Drug repurposing: Progress, challenges and recommendations","volume":"18","author":"Pushpakom","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3626","DOI":"10.1021\/jm501844d","article-title":"Approved Drugs Containing Thiols as Inhibitors of Metallo-\u03b2-lactamases: Strategy To Combat Multidrug-Resistant Bacteria","volume":"58","author":"Klingler","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.bmcl.2013.10.068","article-title":"Simplified captopril analogues as NDM-1 inhibitors","volume":"24","author":"Li","year":"2014","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.jtemb.2019.05.003","article-title":"Heavy metal toxicity: An update of chelating therapeutic strategies","volume":"54","author":"Kim","year":"2019","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1146\/annurev.pa.23.040183.001205","article-title":"V DMSA and DMPS-Water Soluble Antidotes for Heavy Metal Poisoning","volume":"23","author":"Aposhian","year":"1983","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_37","first-page":"8","article-title":"DMPS (2,3-Dimercaptopropane-1-sulfonate, Dimaval) Decreases the Body Burden of Mercury in Humans Exposed to Mercurous Chloride","volume":"287","author":"Hurlbut","year":"1998","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1021\/bi027072i","article-title":"Thiols as Classical and Slow-Binding Inhibitors of IMP-1 and Other Binuclear Metallo-\u03b2-lactamases","volume":"42","author":"Siemann","year":"2003","journal-title":"Biochemistry"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1007\/s13238-011-1055-9","article-title":"A structural view of the antibiotic degradation enzyme NDM-1 from a superbug","volume":"2","author":"Guo","year":"2011","journal-title":"Protein Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"10983","DOI":"10.1021\/ic401072d","article-title":"Zinc Coordination Spheres in Protein Structures","volume":"52","author":"Laitaoja","year":"2013","journal-title":"Inorg. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.ejmech.2018.01.032","article-title":"((S)-3-Mercapto-2-methylpropanamido)acetic acid derivatives as metallo-\u03b2-lactamase inhibitors: Synthesis, kinetic and crystallographic studies","volume":"145","author":"Lui","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"11362","DOI":"10.1021\/ja303579d","article-title":"New Delhi Metallo-\u03b2-Lactamase: Structural Insights into \u03b2-Lactam Recognition and Inhibition","volume":"134","author":"King","year":"2012","journal-title":"J. Am. Chem. Soc."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"7160","DOI":"10.1021\/acs.jmedchem.9b00735","article-title":"Structure-Based Development of (1-(3\u2032-Mercaptopropanamido)methyl)boronic Acid Derived Broad-Spectrum, Dual-Action Inhibitors of Metallo- and Serine-\u03b2-lactamases","volume":"62","author":"Wang","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1016\/j.bcp.2007.05.021","article-title":"Metallo-\u03b2-lactamases (classification, activity, genetic organization, structure, zinc coordination) and their superfamily","volume":"74","author":"Bebrone","year":"2007","journal-title":"Biochem. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"eaay8314","DOI":"10.1126\/scitranslmed.aay8314","article-title":"Preclinical validation of a repurposed metal chelator as an early-intervention therapeutic for hemotoxic snakebite","volume":"12","author":"Albulescu","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Xie, C., Albulescu, L.-O., Bittenbinder, M.A., Somsen, G.W., Vonk, F.J., Casewell, N.R., and Kool, J. (2020). Neutralizing Effects of Small Molecule Inhibitors and Metal Chelators on Coagulopathic Viperinae Snake Venom Toxins. Biomedicines, 8.","DOI":"10.1101\/2020.06.02.129643"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e01579-18","DOI":"10.1128\/AAC.01579-18","article-title":"Active-Site Conformational Fluctuations Promote the Enzymatic Activity of NDM-1","volume":"62","author":"Zhang","year":"2018","journal-title":"Antimicrob. Agents. Chemother."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"104","DOI":"10.3103\/S0027131416020048","article-title":"Cloning and expression of NDM-1 metallo-\u03b2-lactamase gene and study of the catalytic properties of the recombinant enzyme","volume":"71","author":"Grigorenko","year":"2016","journal-title":"Mosc. Univ. Chem. Bull."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1080\/20477724.2018.1460949","article-title":"Comparative analysis of Klebsiella pneumoniae strains isolated in 2012\u20132016 that differ by antibiotic resistance genes and virulence genes profiles","volume":"112","author":"Lev","year":"2018","journal-title":"Pathog. Glob. Health"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"044130","DOI":"10.1063\/5.0014475","article-title":"Scalable molecular dynamics on CPU and GPU architectures with NAMD","volume":"153","author":"Phillips","year":"2020","journal-title":"J. Chem. Phys."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3257","DOI":"10.1021\/ct300400x","article-title":"Optimization of the Additive CHARMM All-Atom Protein Force Field Targeting Improved Sampling of the Backbone \u03d5, \u03c8 and Side-Chain \u03c71 and \u03c72 Dihedral Angles","volume":"8","author":"Best","year":"2012","journal-title":"J. Chem. Theory Comput."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1063\/1.445869","article-title":"Comparison of simple potential functions for simulating liquid water","volume":"79","author":"Jorgensen","year":"1983","journal-title":"J. Chem. Phys."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1002\/jcc.21367","article-title":"CHARMM general force field (CGenFF): A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields","volume":"31","author":"Vanommeslaeghe","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"6158","DOI":"10.1063\/1.478522","article-title":"Toward reliable density functional methods without adjustable parameters: The PBE0 model","volume":"110","author":"Adamo","year":"1999","journal-title":"J. Chem. Phys."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"154104","DOI":"10.1063\/1.3382344","article-title":"A consistent and accurate ab initio parametrization of density functional dispersion correction (DFT-D) for the 94 elements H-Pu","volume":"132","author":"Grimme","year":"2010","journal-title":"J. Chem. Phys."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1038\/nmeth.4638","article-title":"NAMD goes quantum: An integrative suite for QM\/MM simulations","volume":"15","author":"Melo","year":"2018","journal-title":"Nat. Methods"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e1494","DOI":"10.1002\/wcms.1494","article-title":"TeraChem: A graphical processing unit-accelerated electronic structure package for large-scale ab initio molecular dynamics","volume":"11","author":"Seritan","year":"2021","journal-title":"WIREs Comput. Mol. Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/3\/1834\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:14:55Z","timestamp":1760134495000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/3\/1834"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,6]]},"references-count":57,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["ijms23031834"],"URL":"https:\/\/doi.org\/10.3390\/ijms23031834","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,6]]}}}