{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T05:17:08Z","timestamp":1788585428315,"version":"build-2803163510"},"reference-count":65,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:00:00Z","timestamp":1787961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by excessive extracellular matrix remodeling and limited therapeutic options. Matrix metalloproteinase-2 is involved in extracellular matrix degradation and tissue remodeling, making it a relevant target for antifibrotic drug discovery. In this study, an MMP2-focused ligand-based pharmacophore model was developed and was applied to screen a curated FDA-approved drug library, leading to the identification of 83 pharmacophore-matching compounds. These compounds were subsequently prioritized through molecular docking against the catalytic site of MMP2, and the five best candidates were further evaluated by molecular dynamics (MD) simulations. Because of the biological relevance of MMP3 in pulmonary fibrosis, these five selected compounds were also profiled against MMP3 as a secondary target. Among them, Regorafenib (S1178) and Capmatinib (S2788) showed the most favorable cross-target profiles and were further supported by MD analysis. From these findings, S1178 and S2788 were proposed as promising MMP2-prioritized compounds with potential MMP3 cross-activity, warranting further experimental validation as candidate antifibrotic MMP modulators.<\/jats:p>","DOI":"10.3390\/ijms27177756","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T09:48:36Z","timestamp":1788256116000},"page":"7756","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Computational Repurposing of FDA-Approved Drugs as Candidate MMP2 Inhibitors with Putative MMP3 Cross-Activity"],"prefix":"10.3390","volume":"27","author":[{"given":"Saad","family":"Zekri","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Chemistry, Faculty of Sciences Semlalia, Cadi Ayyad University, UCA, B.P. 2390, Marrakech 40000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0629-4321","authenticated-orcid":false,"given":"Nouhaila","family":"Ait Lahcen","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Chemistry, Faculty of Sciences Semlalia, Cadi Ayyad University, UCA, B.P. 2390, Marrakech 40000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wissal","family":"Liman","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Chemistry, Faculty of Sciences Semlalia, Cadi Ayyad University, UCA, B.P. 2390, Marrakech 40000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5839-4298","authenticated-orcid":false,"given":"Francesca","family":"Bianchini","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d, Section of Experimental Pathology and Oncology, University of Florence, 50141 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2465-0537","authenticated-orcid":false,"given":"Mehdi","family":"Oubahmane","sequence":"additional","affiliation":[{"name":"Mohammed VI Polytechnic University (UM6P), Hay Moulay Rachid, Ben Guerir 43150, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1435-5131","authenticated-orcid":false,"given":"Ismail","family":"Hdoufane","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Chemistry, Faculty of Sciences Semlalia, Cadi Ayyad University, UCA, B.P. 2390, Marrakech 40000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Driss","family":"Cherqaoui","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Chemistry, Faculty of Sciences Semlalia, Cadi Ayyad University, UCA, B.P. 2390, Marrakech 40000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"00362","DOI":"10.1183\/23120541.00362-2025","article-title":"Global Trends in Idiopathic Pulmonary Fibrosis Mortality Rates during 2001\u20132022","volume":"11","author":"Harada","year":"2025","journal-title":"ERJ Open Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1007\/s13665-018-0210-7","article-title":"Risk Factors for the Development of Idiopathic Pulmonary Fibrosis: A Review","volume":"7","author":"Zaman","year":"2018","journal-title":"Curr. Pulmonol. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S16","DOI":"10.1513\/AnnalsATS.201410-448MG","article-title":"Mechanisms of Alveolar Epithelial Injury, Repair, and Fibrosis","volume":"12","author":"Chambers","year":"2015","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.drudis.2019.07.013","article-title":"Understanding the Variability of the S1\u2032 Pocket to Improve Matrix Metalloproteinase Inhibitor Selectivity Profiles","volume":"25","author":"Gimeno","year":"2020","journal-title":"Drug Discov. Today"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"117044","DOI":"10.1016\/j.bmc.2022.117044","article-title":"A Review of MMP-2 Structures and Binding Mode Analysis of Its Inhibitors to Strategize Structure-Based Drug Design","volume":"74","author":"Sanyal","year":"2022","journal-title":"Bioorg. Med. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/j.1742-4658.2010.07919.x","article-title":"Roles of Matrix Metalloproteinases in Cancer Progression and Their Pharmacological Targeting","volume":"278","author":"Gialeli","year":"2011","journal-title":"FEBS J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"113044","DOI":"10.1016\/j.ejmech.2020.113044","article-title":"Outline of Gelatinase Inhibitors as Anti-Cancer Agents: A Patent Mini-Review for 2010-Present","volume":"213","author":"Baidya","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3619","DOI":"10.21873\/anticanres.14351","article-title":"Gene Polymorphisms and Circulating Levels of MMP-2 and MMP-9: A Review of Their Role in Breast Cancer Risk","volume":"40","author":"Dofara","year":"2020","journal-title":"Anticancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Huang, Y., Niu, T., Yang, J., Liu, Y., Chen, Z., Wang, K., Zheng, X., Li, X., and Liu, J. (2026). Elevated MMP2 Expression in Fibrotic Interstitial Lung Disease: A Potential Biomarker for Assessment of Disease Severity. BMC Pulm. Med., 26.","DOI":"10.1186\/s12890-026-04139-9"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1183\/09031936.00060708","article-title":"MMP Expression and Abnormal Lung Permeability Are Important Determinants of Outcome in IPF","volume":"33","author":"McKeown","year":"2009","journal-title":"Eur. Respir. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1186\/s12931-022-02105-7","article-title":"Role of Matrix Metalloprotease-2 and MMP-9 in Experimental Lung Fibrosis in Mice","volume":"23","author":"Bormann","year":"2022","journal-title":"Respir. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s12931-016-0343-6","article-title":"Role of Matrix Metalloproteinases in the Pathogenesis of Idiopathic Pulmonary Fibrosis","volume":"17","author":"Pardo","year":"2016","journal-title":"Respir. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"122874","DOI":"10.1016\/j.lfs.2024.122874","article-title":"MMPs as Potential Molecular Targets in Epithelial-to-Mesenchymal Transition Driven COPD Progression","volume":"352","author":"Agraval","year":"2024","journal-title":"Life Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1016\/j.ajpath.2011.06.041","article-title":"Matrix Metalloproteinase 3 Is a Mediator of Pulmonary Fibrosis","volume":"179","author":"Yamashita","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1056\/NEJMoa1103690","article-title":"Efficacy of a Tyrosine Kinase Inhibitor in Idiopathic Pulmonary Fibrosis","volume":"365","author":"Richeldi","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1016\/S0140-6736(11)60405-4","article-title":"Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis (CAPACITY): Two Randomised Trials","volume":"377","author":"Noble","year":"2011","journal-title":"Lancet"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1056\/NEJMoa2414108","article-title":"Nerandomilast in Patients with Idiopathic Pulmonary Fibrosis","volume":"392","author":"Richeldi","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Giordano, D., Biancaniello, C., Argenio, M.A., and Facchiano, A. (2022). Drug Design by Pharmacophore and Virtual Screening Approach. Pharmaceuticals, 15.","DOI":"10.3390\/ph15050646"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Maia, E.H.B., Assis, L.C., De Oliveira, T.A., Da Silva, A.M., and Taranto, A.G. (2020). Structure-Based Virtual Screening: From Classical to Artificial Intelligence. Front. Chem., 8.","DOI":"10.3389\/fchem.2020.00343"},{"key":"ref_20","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_21","doi-asserted-by":"crossref","first-page":"195","DOI":"10.4103\/tjem.tjem_182_23","article-title":"Receiver Operating Characteristic Curve Analysis in Diagnostic Accuracy Studies: A Guide to Interpreting the Area under the Curve Value","volume":"23","author":"Aksel","year":"2023","journal-title":"Turk. J. Emerg. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"109487","DOI":"10.1016\/j.compbiomed.2024.109487","article-title":"Potential Matrix Metalloproteinase 2 and 9 Inhibitors Identified from Ehretia Species for the Treatment of Chronic Wounds\u2014Computational Drug Discovery Approaches","volume":"185","author":"Oselusi","year":"2025","journal-title":"Comput. Biol. Med."},{"key":"ref_23","first-page":"298","article-title":"Molecular Docking and Inhibition of Matrix Metalloproteinase-2 by Novel Difluorinatedbenzylidene Curcumin Analog","volume":"7","author":"Ahmad","year":"2015","journal-title":"Am. J. Transl. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6750","DOI":"10.1016\/j.bmcl.2007.10.042","article-title":"A Novel Series of Highly Selective Inhibitors of MMP-3","volume":"17","author":"Whitlock","year":"2007","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1038\/sj.bjc.6603043","article-title":"Towards Third Generation Matrix Metalloproteinase Inhibitors for Cancer Therapy","volume":"94","author":"Overall","year":"2006","journal-title":"Br. J. Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1158\/1535-7163.MCT-17-0646","article-title":"Matrix Metalloproteinase Inhibitors in Cancer Therapy: Turning Past Failures Into Future Successes","volume":"17","author":"Winer","year":"2018","journal-title":"Mol. Cancer Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s11523-014-0333-x","article-title":"Regorafenib as a Single-Agent in the Treatment of Patients with Gastrointestinal Tumors: An Overview for Pharmacists","volume":"10","author":"Rey","year":"2015","journal-title":"Target. Oncol."},{"key":"ref_28","unstructured":"U.S. Food and Drug Administration (2026, August 08). STIVARGA (Regorafenib) Prescribing Information, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2017\/203085s007lbl.pdf."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"33","DOI":"10.2147\/LCTT.S360574","article-title":"Spotlight on Tepotinib and Capmatinib for Non-Small Cell Lung Cancer with MET Exon 14 Skipping Mutation","volume":"13","author":"Brazel","year":"2022","journal-title":"Lung Cancer Targets Ther."},{"key":"ref_30","unstructured":"U.S. Food and Drug Administration (2026, August 08). TABRECTA (Capmatinib) Prescribing Information, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/Nda\/2020\/213591Orig1s000lbl.pdf."},{"key":"ref_31","unstructured":"DailyMed (2026, August 20). STIVARGA- Regorafenib Tablet, Film Coated, Available online: https:\/\/dailymed.nlm.nih.gov\/dailymed\/drugInfo.cfm?setid=824f19c9-0546-4a8a-8d8f-c4055c04f7c7&utm_source=chatgpt.com."},{"key":"ref_32","unstructured":"DailyMed (2026, August 20). NEXAVAR- Sorafenib Tablet, Film Coated, Available online: https:\/\/dailymed.nlm.nih.gov\/dailymed\/lookup.cfm?Setid=b50667e4-5ebc-4968-A646-D605058dbef0."},{"key":"ref_33","unstructured":"DailyMed (2026, August 20). INLYTA- Axitinib Tablet, Film Coated, Available online: https:\/\/dailymed.nlm.nih.gov\/dailymed\/drugInfo.cfm?Setid=8a903e31-936e-4ed7-8a59-59f32374f338."},{"key":"ref_34","unstructured":"DailyMed (2026, August 20). TAFINLAR- Dabrafenib Capsule TAFINLAR- Dabrafenib Tablet, for Suspension, Available online: https:\/\/dailymed.nlm.nih.gov\/dailymed\/drugInfo.Cfm?Setid=fee1e6b1-E1a5-4254-9f2e-A70e0f8dbdea."},{"key":"ref_35","unstructured":"DailyMed (2026, August 20). TABRECTA- Capmatinib Tablet, Film Coated, Available online: https:\/\/dailymed.nlm.nih.gov\/dailymed\/drugInfo.Cfm?Audience=consumer&setid=455892c3-D144-4ba8-9ab4-79cabff9876d."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4664","DOI":"10.1016\/j.bmcl.2015.08.026","article-title":"Sulfonamide Derivatives Containing Dihydropyrazole Moieties Selectively and Potently Inhibit MMP-2\/MMP-9: Design, Synthesis, Inhibitory Activity and 3D-QSAR Analysis","volume":"25","author":"Yan","year":"2015","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_37","unstructured":"ChemDraw (2026, January 01). Revvity Signals Software. Available online: https:\/\/revvitysignals.com\/Products\/Research\/Chemdraw."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6582","DOI":"10.1021\/jm300687e","article-title":"Directory of Useful Decoys, Enhanced (DUD-E): Better Ligands and Decoys for Better Benchmarking","volume":"55","author":"Mysinger","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_39","unstructured":"Selleckchem Library (2026, February 01). FDA-Approved Drug Library. Available online: https:\/\/www.selleckchem.com\/screening\/Fda-Approved-Drug-Library.html."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1021\/ci049885e","article-title":"LigandScout: 3-D Pharmacophores Derived from Protein-Bound Ligands and Their Use as Virtual Screening Filters","volume":"45","author":"Wolber","year":"2005","journal-title":"J. Chem. Inf. Model."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.ymeth.2014.10.013","article-title":"Methods for Generating and Applying Pharmacophore Models as Virtual Screening Filters and for Bioactivity Profiling","volume":"71","author":"Vuorinen","year":"2015","journal-title":"Methods"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.biosystems.2017.09.005","article-title":"Toward a Hierarchical Virtual Screening and Toxicity Risk Analysis for Identifying Novel CA XII Inhibitors","volume":"162","author":"Nazarshodeh","year":"2017","journal-title":"Biosystems"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.biosystems.2013.12.002","article-title":"Pharmacophore Mapping-Based Virtual Screening Followed by Molecular Docking Studies in Search of Potential Acetylcholinesterase Inhibitors as Anti-Alzheimer\u2019s Agents","volume":"116","author":"Ambure","year":"2014","journal-title":"Biosystems"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1423-0127-18-8","article-title":"The Discovery of Potential Acetylcholinesterase Inhibitors: A Combination of Pharmacophore Modeling, Virtual Screening, and Molecular Docking Studies","volume":"18","author":"Lu","year":"2011","journal-title":"J. Biomed. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2328","DOI":"10.1007\/s00044-012-0227-3","article-title":"New Molecular Scaffolds for the Design of Alzheimer\u2019s Acetylcholinesterase Inhibitors Identified Using Ligand- and Receptor-Based Virtual Screening","volume":"22","author":"Chitranshi","year":"2013","journal-title":"Med. Chem. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/S0167-4838(02)00307-2","article-title":"Solution Structure and Backbone Dynamics of the Catalytic Domain of Matrix Metalloproteinase-2 Complexed with a Hydroxamic Acid Inhibitor","volume":"1598","author":"Feng","year":"2002","journal-title":"Biochim. Biophys. Acta Proteins Proteom."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1021\/jm960465t","article-title":"Inhibition of Stromelysin-1 (MMP-3) by P1 \u2018-Biphenylylethyl Carboxyalkyl Dipeptides","volume":"40","author":"Esser","year":"1997","journal-title":"J. Med. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"W368","DOI":"10.1093\/nar\/gki464","article-title":"H++: A Server for Estimating pKas and Adding Missing Hydrogens to Macromolecules","volume":"33","author":"Gordon","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1002\/jcc.21256","article-title":"AutoDock4 and AutoDockTools4: Automated Docking with Selective Receptor Flexibility","volume":"30","author":"Morris","year":"2009","journal-title":"J. Comput. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the Speed and Accuracy of Docking with a New Scoring Function, Efficient Optimization, and Multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e1298","DOI":"10.1002\/wcms.1298","article-title":"Using PyMOL as a Platform for Computational Drug Design","volume":"7","author":"Yuan","year":"2017","journal-title":"WIREs Comput. Mol. Sci."},{"key":"ref_52","unstructured":"Dassault Syst\u00e8mes (2026, February 15). BIOVIA Discovery Studio Visualizer. Available online: https:\/\/discover.3ds.com\/Discovery-Studio-Visualizer-Download."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2281","DOI":"10.1021\/acs.jcim.6b00283","article-title":"Screening Explorer\u2013An Interactive Tool for the Analysis of Screening Results","volume":"56","author":"Zagury","year":"2016","journal-title":"J. Chem. Inf. Model."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1002\/jcc.20291","article-title":"GROMACS: Fast, Flexible, and Free","volume":"26","author":"Lindahl","year":"2005","journal-title":"J. Comput. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/nmeth.4067","article-title":"CHARMM36m: An Improved Force Field for Folded and Intrinsically Disordered Proteins","volume":"14","author":"Huang","year":"2017","journal-title":"Nat. Methods"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1002\/jcc.21367","article-title":"CHARMM General Force Field: 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_57","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1002\/prot.340230104","article-title":"Zinc Binding in Proteins and Solution: A Simple but Accurate Nonbonded Representation","volume":"23","author":"Stote","year":"1995","journal-title":"Proteins"},{"key":"ref_58","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_59","doi-asserted-by":"crossref","first-page":"10089","DOI":"10.1063\/1.464397","article-title":"Particle Mesh Ewald: An N\u22c5log(N) Method for Ewald Sums in Large Systems","volume":"98","author":"Darden","year":"1993","journal-title":"J. Chem. Phys."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1002\/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.0.CO;2-H","article-title":"LINCS: A Linear Constraint Solver for Molecular Simulations","volume":"18","author":"Hess","year":"1997","journal-title":"J. Comput. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"014101","DOI":"10.1063\/1.2408420","article-title":"Canonical Sampling through Velocity Rescaling","volume":"126","author":"Bussi","year":"2007","journal-title":"J. Chem. Phys."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"124108","DOI":"10.1063\/1.4978807","article-title":"Application of Berendsen Barostat in Dissipative Particle Dynamics for Nonequilibrium Dynamic Simulation","volume":"146","author":"Lin","year":"2017","journal-title":"J. Chem. Phys."},{"key":"ref_63","unstructured":"GRACE (2026, March 01). GRaphing, Advanced Computation and Exploration of Data. Available online: https:\/\/plasma-gate.weizmann.ac.il\/Grace\/."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"6281","DOI":"10.1021\/acs.jctc.1c00645","article-title":"gmx_MMPBSA: A New Tool to Perform End-State Free Energy Calculations with GROMACS","volume":"17","author":"Valiente","year":"2021","journal-title":"J. Chem. Theory Comput."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1007\/s11227-025-07858-8","article-title":"TOUBKAL: A High-Performance Supercomputer Powering Scientific Research in Africa","volume":"81","author":"Kissami","year":"2025","journal-title":"J. Supercomput."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7756\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T04:47:57Z","timestamp":1788583677000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7756"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,29]]},"references-count":65,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ijms27177756"],"URL":"https:\/\/doi.org\/10.3390\/ijms27177756","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,29]]}}}