{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T18:14:55Z","timestamp":1783707295557,"version":"3.55.0"},"reference-count":64,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004242","name":"Princess Nourah Bint Abdulrahman University","doi-asserted-by":"publisher","award":["PNURSP2026R150"],"award-info":[{"award-number":["PNURSP2026R150"]}],"id":[{"id":"10.13039\/501100004242","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Lung cancer is one of the leading causes of cancer-related deaths globally, with smoking being the primary risk factor, though environmental exposures and genetic mutations also play significant roles. Lung cancer arises when abnormal lung cells grow uncontrollably, leading to over 2 million new cases and nearly 1.8 million deaths globally. Drug resistance, especially to targeted therapies, is a key challenge, as tumours often adapt and become unresponsive. Multitargeted drug design, which targets multiple pathways involved in tumour growth, offers a promising solution to overcome resistance and improve treatment efficacy. In this study, we identified several lung cancer\u2013associated proteins: CK2, Ran\u2013Importin \u03b2 complex, HNGF, Human Survivin, CRK-II adaptor protein, AKR1B10, and tRNA dihydrouridine synthase 2, with respective PDB IDs 1JWH, 1IBR, 1SG1, 1XOX, 2DVJ, 4XZL, and 4XP7. We conducted molecular docking using DrugBank\u2019s library, employing HTVS, SP, and XP, followed by pose processing with MM\/GBSA. Our multitarget docking analysis identified\n                    <jats:italic>Quercetin-3-O-Phosphate<\/jats:italic>\n                    as the top compound, a quercetin derivative found in fruits and vegetables such as onions, apples, berries, broccoli, and citrus. The compound showed docking and MM\/GBSA scores ranging from \u22125.835 to \u221211.627 Kcal\/mol and \u221214.28 to \u221247.07 Kcal\/mol, respectively, and the key interacting residues with their counts include 10ASP, 9LEU, 9LYS, 7ALA, 7ARG, 7TYR, 6GLN, 5ASN, 5GLU, 5ILE, and 5VAL. We also performed and analysed DFT and pharmacokinetics in detail, which supported its further evaluation as it met all the required criteria. We conducted a 5 ns WaterMap simulation, which confirmed the interactions and highlighted key hydration sites that support the complex\u2019s stability. A 100 ns MD simulation using the TIP3P water model showed minimal deviation and fluctuations, indicating stable interactions and the trajectories used for MM\/GBSA calculations, assessing binding free, which reinforced the stability of the complexes and helped rank the best candidates. All results indicate that Quercetin-3-O-Phosphate holds strong potential for lung cancer treatment, though experimental validation is needed for clinical confirmation.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0349042","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T17:28:54Z","timestamp":1783704534000},"page":"e0349042","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Heptapharmacological activity of Quercetin-3-O-phosphate against lung cancer pathways"],"prefix":"10.1371","volume":"21","author":[{"given":"Maryam Abdulrahman","family":"Alahdal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3075-5514","authenticated-orcid":true,"given":"Hadil","family":"Alahdal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Najat","family":"Binothman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Majidah","family":"Aljadani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5460-1440","authenticated-orcid":true,"given":"Nawal","family":"Helmi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam A.","family":"AL-Ghamdi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa Hamed","family":"Habib","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misbahuddin","family":"Rafeeq","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5379-1385","authenticated-orcid":true,"given":"Tahani","family":"Bakhsh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadeel A.","family":"Alsufyani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7851-4365","authenticated-orcid":true,"given":"Abeer","family":"Al Tuwaijri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"issue":"6","key":"pone.0349042.ref001","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1080\/1061186X.2024.2347358","article-title":"An extensive review on lung cancer therapeutics using machine learning techniques: state-of-the-art and perspectives","volume":"32","author":"S Ahmad","year":"2024","journal-title":"J Drug Target"},{"issue":"9","key":"pone.0349042.ref002","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1038\/s41571-023-00798-3","article-title":"The global burden of lung cancer: current status and future trends","volume":"20","author":"A Leiter","year":"2023","journal-title":"Nat Rev Clin Oncol"},{"issue":"1","key":"pone.0349042.ref003","doi-asserted-by":"crossref","first-page":"8","DOI":"10.5334\/aogh.2419","article-title":"Global Epidemiology of Lung Cancer","volume":"85","author":"JA Barta","year":"2019","journal-title":"Ann Glob Health"},{"issue":"1","key":"pone.0349042.ref004","doi-asserted-by":"crossref","DOI":"10.2174\/1874079001508010001","article-title":"Tobacco consumption and oral, pharyngeal and lung cancers","volume":"8","author":"MA Bassiony","year":"2015","journal-title":"The Open Cancer Journal"},{"issue":"7","key":"pone.0349042.ref005","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1002\/ijc.35278","article-title":"The GLOBOCAN 2022 cancer estimates: Data sources, methods, and a snapshot of the cancer burden worldwide","volume":"156","author":"AM Filho","year":"2025","journal-title":"Int J Cancer"},{"key":"pone.0349042.ref006","doi-asserted-by":"crossref","DOI":"10.4103\/ijc.IJC_449_19","article-title":"Molecularly targeted therapies in non-small cell lung cancer: The evolving role of tyrosine kinase inhibitors","volume":"56","author":"DC Doval","year":"2019","journal-title":"Indian J Cancer"},{"issue":"1","key":"pone.0349042.ref007","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s40880-016-0135-x","article-title":"Epidemiology of lung cancer and approaches for its prediction: a systematic review and analysis","volume":"35","author":"AK Dubey","year":"2016","journal-title":"Chin J Cancer"},{"issue":"1","key":"pone.0349042.ref008","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00408-025-00801-x","article-title":"Update 2025: Management of non-small-cell lung cancer","volume":"203","author":"H Jeon","year":"2025","journal-title":"Lung"},{"key":"pone.0349042.ref009","doi-asserted-by":"crossref","first-page":"107438","DOI":"10.1016\/j.pharmthera.2019.107438","article-title":"Drug resistance to targeted therapeutic strategies in non-small cell lung cancer","volume":"206","author":"W-J Liu","year":"2020","journal-title":"Pharmacol Ther"},{"issue":"6","key":"pone.0349042.ref010","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1016\/j.molonc.2014.06.005","article-title":"Tumour heterogeneity and the evolution of polyclonal drug resistance","volume":"8","author":"RA Burrell","year":"2014","journal-title":"Mol Oncol"},{"key":"pone.0349042.ref011","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/978-981-19-8249-1_13","article-title":"Therapeutic Protein-Based Vaccines","author":"S Ahmad","year":"2023","journal-title":"Protein-based Therapeutics. Springer Nature Singapore"},{"issue":"1","key":"pone.0349042.ref012","doi-asserted-by":"crossref","first-page":"16545","DOI":"10.1038\/s41598-023-43789-1","article-title":"In-silico and in-vitro study reveals ziprasidone as a potential aromatase inhibitor against breast carcinoma","volume":"13","author":"A Sahu","year":"2023","journal-title":"Sci Rep"},{"issue":"5","key":"pone.0349042.ref013","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1159\/000443368","article-title":"Drug Resistance to EGFR Inhibitors in Lung Cancer","volume":"61","author":"O Tetsu","year":"2016","journal-title":"Chemotherapy"},{"key":"pone.0349042.ref014","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/B978-0-323-90608-1.00001-0","article-title":"Fundamentals of molecular modeling in drug design","volume-title":"Computer Aided Drug Design (CADD): From ligand-based methods to structure-based approaches","author":"MK Tripathi","year":"2022"},{"key":"pone.0349042.ref015","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/B978-0-443-22299-3.00012-8","article-title":"Deep learning in computer-aided drug design: a case study","author":"S Ahmad","year":"2024","journal-title":"Deep Learning Applications in Translational Bioinformatics. Elsevier"},{"key":"pone.0349042.ref016","doi-asserted-by":"crossref","first-page":"133872","DOI":"10.1016\/j.ijbiomac.2024.133872","article-title":"Reporting multitargeted potency of Tiaprofenic acid against lung cancer: Molecular fingerprinting, MD simulation, and MTT-based cell viability assay studies","volume":"276","author":"S Ahmad","year":"2024","journal-title":"Int J Biol Macromol"},{"issue":"7","key":"pone.0349042.ref017","doi-asserted-by":"crossref","DOI":"10.1177\/1934578X221115499","article-title":"Multitargeted Molecular Dynamic Understanding of Butoxypheser Against SARS-CoV-2: An in Silico Study","volume":"17","author":"S Ahmad","year":"2022","journal-title":"Natural Product Communications"},{"key":"pone.0349042.ref018","doi-asserted-by":"crossref","first-page":"142343","DOI":"10.1016\/j.ijbiomac.2025.142343","article-title":"Probing the multitargeted potency of Theodrenaline and its comparative evaluation with Crizotinib against transferase, hydrolase, signalling, and apoptosis-related proteins to overcome lung cancer drug resistance","volume":"308","author":"S Ahmad","year":"2025","journal-title":"Int J Biol Macromol"},{"issue":"9","key":"pone.0349042.ref019","doi-asserted-by":"crossref","first-page":"4013","DOI":"10.1080\/07391102.2022.2060308","article-title":"Reporting dinaciclib and theodrenaline as a multitargeted inhibitor against SARS-CoV-2: an in-silico study","volume":"41","author":"S Ahmad","year":"2023","journal-title":"J Biomol Struct Dyn"},{"key":"pone.0349042.ref020","doi-asserted-by":"crossref","first-page":"141703","DOI":"10.1016\/j.ijbiomac.2025.141703","article-title":"Evaluating the polypharmacological potency of FEDPN from ChEMBL BioAssays against lung cancer EGFR, ALK, TrkA and KRAS proteins","volume":"306","author":"S Ahmad","year":"2025","journal-title":"Int J Biol Macromol"},{"key":"pone.0349042.ref021","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/B978-0-443-13222-3.00007-1","article-title":"Application of machine learning\u2013based approaches in stem cell research","volume-title":"Computational biology for stem cell research","author":"MK Yadav","year":"2024"},{"issue":"5","key":"pone.0349042.ref022","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1080\/07391102.2021.2021993","article-title":"Predictive modeling and therapeutic repurposing of natural compounds against the receptor-binding domain of SARS-CoV-2","volume":"41","author":"MK Yadav","year":"2023","journal-title":"J Biomol Struct Dyn"},{"issue":"19","key":"pone.0349042.ref023","doi-asserted-by":"crossref","first-page":"5320","DOI":"10.1093\/emboj\/20.19.5320","article-title":"Crystal structure of human protein kinase CK2: insights into basic properties of the CK2 holoenzyme","volume":"20","author":"K Niefind","year":"2001","journal-title":"EMBO J"},{"issue":"5","key":"pone.0349042.ref024","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/S0092-8674(00)80774-6","article-title":"Structural view of the Ran-Importin beta interaction at 2.3 A resolution","volume":"97","author":"IR Vetter","year":"1999","journal-title":"Cell"},{"issue":"5672","key":"pone.0349042.ref025","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1126\/science.1095190","article-title":"Structure of nerve growth factor complexed with the shared neurotrophin receptor p75","volume":"304","author":"X-L He","year":"2004","journal-title":"Science"},{"issue":"1","key":"pone.0349042.ref026","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1021\/bi0485171","article-title":"Solution structure of human survivin and its binding interface with Smac\/Diablo","volume":"44","author":"C Sun","year":"2005","journal-title":"Biochemistry"},{"issue":"6","key":"pone.0349042.ref027","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/nsmb1241","article-title":"Structural basis for the transforming activity of human cancer-related signaling adaptor protein CRK","volume":"14","author":"Y Kobashigawa","year":"2007","journal-title":"Nat Struct Mol Biol"},{"issue":"12","key":"pone.0349042.ref028","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1002\/cmdc.201500393","article-title":"Structural Determinants of the Selectivity of 3-Benzyluracil-1-acetic Acids toward Human Enzymes Aldose Reductase and AKR1B10","volume":"10","author":"FX Ruiz","year":"2015","journal-title":"ChemMedChem"},{"key":"pone.0349042.ref029","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1107\/S1399004715009220","article-title":"From bacterial to human dihydrouridine synthase: automated structure determination","volume":"71","author":"F Whelan","year":"2015","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"pone.0349042.ref030","doi-asserted-by":"crossref","first-page":"110163","DOI":"10.1016\/j.compbiomed.2025.110163","article-title":"FDA-approved Levophed as an alternative multitargeted therapeutic against cervical cancer transferase, cell cycle, and regulatory proteins","volume":"191","author":"N Bano","year":"2025","journal-title":"Comput Biol Med"},{"issue":"6","key":"pone.0349042.ref031","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1021\/ja00214a001","article-title":"The OPLS [optimized potentials for liquid simulations] potential functions for proteins, energy minimizations for crystals of cyclic peptides and crambin","volume":"110","author":"WL Jorgensen","year":"1988","journal-title":"J Am Chem Soc"},{"key":"pone.0349042.ref032","unstructured":"Maestro S, Maestro. New York, NY: Schr\u00f6dinger, LLC. 2024."},{"key":"pone.0349042.ref033","unstructured":"Release S. LigPrep. New York, NY: Schr\u00f6dinger, LLC. 2024."},{"issue":"3","key":"pone.0349042.ref034","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1007\/s42250-023-00604-8","article-title":"Comprehensive Computational Studies of Naturally Occurring Kuguacins as Antidiabetic Agents by Targeting Visfatin","volume":"6","author":"SO Famuyiwa","year":"2023","journal-title":"Chemistry Africa"},{"issue":"12","key":"pone.0349042.ref035","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1007\/s10822-007-9133-z","article-title":"Epik: a software program for pK(a) prediction and protonation state generation for drug-like molecules","volume":"21","author":"JC Shelley","year":"2007","journal-title":"J Comput Aided Mol Des"},{"key":"pone.0349042.ref036","doi-asserted-by":"crossref","first-page":"7","DOI":"10.53388\/MDM202508008","article-title":"RCSB Protein Data Bank: revolutionising drug discovery and design for over five decades","volume":"8","author":"S Ahmad","year":"2025","journal-title":"Medical Data Mining"},{"key":"pone.0349042.ref037","unstructured":"Release S. Schr\u00f6dinger Suite 2024 Protein Preparation Wizard. Epik. New York, NY: Schr\u00f6dinger, LLC. 2024."},{"issue":"2","key":"pone.0349042.ref038","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1002\/prot.10613","article-title":"A hierarchical approach to all-atom protein loop prediction","volume":"55","author":"MP Jacobson","year":"2004","journal-title":"Proteins"},{"issue":"2","key":"pone.0349042.ref039","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1021\/ct100578z","article-title":"PROPKA3: Consistent Treatment of Internal and Surface Residues in Empirical pKa Predictions","volume":"7","author":"MHM Olsson","year":"2011","journal-title":"J Chem Theory Comput"},{"key":"pone.0349042.ref040","volume-title":"Receptor grid generation","author":"S Release","year":"2024"},{"issue":"3","key":"pone.0349042.ref041","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1007\/s11030-023-10648-0","article-title":"Identification of 5-nitroindazole as a multitargeted inhibitor for CDK and transferase kinase in lung cancer: a multisampling algorithm-based structural study","volume":"28","author":"S Ahmad","year":"2024","journal-title":"Mol Divers"},{"issue":"19","key":"pone.0349042.ref042","doi-asserted-by":"crossref","first-page":"9770","DOI":"10.1080\/07391102.2022.2146202","article-title":"In-silico analysis reveals Quinic acid as a multitargeted inhibitor against Cervical Cancer","volume":"41","author":"S Ahmad","year":"2023","journal-title":"J Biomol Struct Dyn"},{"key":"pone.0349042.ref043","doi-asserted-by":"crossref","first-page":"132332","DOI":"10.1016\/j.ijbiomac.2024.132332","article-title":"Integrative analysis discovers Imidurea as dual multitargeted inhibitor of CD69, CD40, SHP2, lysozyme, GATA3, cCBL, and S-cysteinase from SARS-CoV-2 and M. tuberculosis","volume":"270","author":"S Ahmad","year":"2024","journal-title":"Int J Biol Macromol"},{"key":"pone.0349042.ref044","unstructured":"Release S. Glide. NY, USA: Schr\u00f6dinger. 2024."},{"issue":"4","key":"pone.0349042.ref045","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.ddtec.2004.11.007","article-title":"Lead- and drug-like compounds: the rule-of-five revolution","volume":"1","author":"CA Lipinski","year":"2004","journal-title":"Drug Discov Today Technol"},{"key":"pone.0349042.ref046","unstructured":"QikProp S. Schr\u00f6dinger release 2024. New York, USA: Maestro LLC. 2024."},{"issue":"5","key":"pone.0349042.ref047","doi-asserted-by":"crossref","first-page":"2494","DOI":"10.1080\/07391102.2023.2209673","article-title":"Multisampling-based docking reveals Imidazolidinyl urea as a multitargeted inhibitor for lung cancer: an optimisation followed multi-simulation and in-vitro study","volume":"42","author":"S Ahmad","year":"2024","journal-title":"J Biomol Struct Dyn"},{"key":"pone.0349042.ref048","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/B978-0-12-821013-0.00002-7","article-title":"Exosomes as an emerging nanoplatform for functional therapeutics","author":"B Balasubramanian","year":"2021","journal-title":"Handbook on nanobiomaterials for therapeutics and diagnostic applications"},{"key":"pone.0349042.ref049","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.compbiolchem.2018.02.008","article-title":"Multiple grid arrangement improves ligand docking with unknown binding sites: Application to the inverse docking problem","volume":"73","author":"T Ban","year":"2018","journal-title":"Comput Biol Chem"},{"key":"pone.0349042.ref050","doi-asserted-by":"crossref","first-page":"135701","DOI":"10.1016\/j.molstruc.2023.135701","article-title":"Synthesis, single crystal, TD-DFT, molecular dynamics simulation and DNA binding studies of carbothioamide analog","volume":"1287","author":"Nouman","year":"2023","journal-title":"Journal of Molecular Structure"},{"issue":"18","key":"pone.0349042.ref051","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1002\/qua.24481","article-title":"Jaguar: A high\u2010performance quantum chemistry software program with strengths in life and materials sciences","volume":"113","author":"AD Bochevarov","year":"2013","journal-title":"Int J of Quantum Chemistry"},{"key":"pone.0349042.ref052","unstructured":"Release S. Jaguar. New York, NY: Schr\u00f6dinger, LLC. 2024."},{"issue":"5","key":"pone.0349042.ref053","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1021\/acs.jctc.7b00176","article-title":"Assessing DFT-D3 Damping Functions Across Widely Used Density Functionals: Can We Do Better?","volume":"13","author":"J Witte","year":"2017","journal-title":"J Chem Theory Comput"},{"key":"pone.0349042.ref054","volume-title":"A general SCF theory","author":"R Carb\u00f3","year":"2012"},{"issue":"10","key":"pone.0349042.ref055","doi-asserted-by":"crossref","first-page":"5728","DOI":"10.1063\/1.449880","article-title":"Direct inversion in the iterative subspace (DIIS) optimization of open-shell, excited-state, and small multiconfiguration SCF wave functions","volume":"84","author":"TP Hamilton","year":"1986","journal-title":"The Journal of Chemical Physics"},{"key":"pone.0349042.ref056","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/B978-0-12-814421-3.00021-X","article-title":"Computer-aided prediction of pharmacokinetic (ADMET) properties","volume-title":"Dosage form design parameters","author":"B Chandrasekaran","year":"2018"},{"issue":"1","key":"pone.0349042.ref057","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1080\/17460441.2023.2267015","article-title":"The application of WaterMap-guided structure-based virtual screening in novel drug discovery","volume":"19","author":"AA Kaczor","year":"2024","journal-title":"Expert Opin Drug Discov"},{"key":"pone.0349042.ref058","doi-asserted-by":"crossref","unstructured":"Bowers KJ, Sacerdoti FD, Salmon JK, Shan Y, Shaw DE, Chow E, et al. Molecular dynamics---Scalable algorithms for molecular dynamics simulations on commodity clusters. In: Proceedings of the 2006 ACM\/IEEE conference on Supercomputing - SC \u201906, 2006. 84. https:\/\/doi.org\/10.1145\/1188455.1188544","DOI":"10.1145\/1188455.1188544"},{"key":"pone.0349042.ref059","unstructured":"Release S. Desmond molecular dynamics system. New York, NY: DE Shaw research. 2024."},{"issue":"43","key":"pone.0349042.ref060","doi-asserted-by":"crossref","first-page":"9954","DOI":"10.1021\/jp003020w","article-title":"Structure and dynamics of the TIP3P, SPC, and SPC\/E water models at 298 K","volume":"105","author":"P Mark","year":"2001","journal-title":"The Journal of Physical Chemistry A"},{"issue":"1","key":"pone.0349042.ref061","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1080\/00268977200100031","article-title":"NpT-ensemble Monte Carlo calculations for binary liquid mixtures","volume":"23","author":"I McDonald","year":"1972","journal-title":"Molecular Physics"},{"issue":"11","key":"pone.0349042.ref062","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1080\/17460441.2021.1942836","article-title":"What is the current value of MM\/PBSA and MM\/GBSA methods in drug discovery?","volume":"16","author":"T Tuccinardi","year":"2021","journal-title":"Expert Opinion on Drug Discovery"},{"issue":"16","key":"pone.0349042.ref063","doi-asserted-by":"crossref","first-page":"9478","DOI":"10.1021\/acs.chemrev.9b00055","article-title":"End-Point Binding Free Energy Calculation with MM\/PBSA and MM\/GBSA: Strategies and Applications in Drug Design","volume":"119","author":"E Wang","year":"2019","journal-title":"Chem Rev"},{"key":"pone.0349042.ref064","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/978-981-19-9605-4_3","article-title":"Natural Product-Based Drug Designing for Treatment of Human Parasitic Diseases","author":"S Ahmad","year":"2023","journal-title":"Natural Product Based Drug Discovery Against Human Parasites. Springer Nature Singapore"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0349042","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T17:29:04Z","timestamp":1783704544000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0349042"}},"subtitle":[],"editor":[{"given":"Javed","family":"Iqbal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,7,10]]},"references-count":64,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7,10]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0349042","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,10]]}}}