{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T15:14:42Z","timestamp":1792595682857,"version":"4.5.0"},"reference-count":133,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Calotropis procera, a drought-tolerant shrub widely used in folk medicine, was evaluated for its antimicrobial potential and safety using an integrative in vitro\/in silico workflow. Ethanolic leaf extract (EE-CP) displayed a dose-dependent inhibition of Staphylococcus aureus ATCC 2913 and Escherichia coli ATCC 35218, reaching 93% and 52% of the amoxicillin control, respectively (MIC 207 \u00b5g mL\u22121 and 149 \u00b5g mL\u22121). GC-MS and LC-HRMS profiling revealed cardenolides (strophanthidin, gitoxigenin) and indole derivatives as major constituents. Pharmacophore mapping highlighted the essential glycosyltransferase MurG as a likely bacterial target; molecular docking showed that strophanthidin and NCGC00384918 bind MurG more strongly than the native substrate UDP-GlcNAc (\u0394G \u2264 \u22129.4 kcal mol\u22121), a result corroborated by 100 ns molecular dynamics simulations and MM-PBSA binding energies (\u221296.4 and \u221249.3 kcal mol\u22121). EE-CP caused &lt;10% hemolysis up to 1.5 mg mL\u22121 and exhibited LC50 values of 302 \u00b5g mL\u22121 (human lymphocytes) and 247 \u00b5g mL\u22121 (BHK-21 cells), indicating a narrow but exploitable therapeutic window. Collectively, these findings constitute the first report on Colombian C. procera demonstrating potent anti-Staphylococcus activity, MurG-targeted cardenolides, and acceptable erythrocyte compatibility. This study supports EE-CP as a promising source of lead molecules and antibiotic adjuvants, warranting guided fractionation and in vivo validation to optimize efficacy and mitigate cytotoxicity.<\/jats:p>","DOI":"10.3390\/ijms262110574","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T01:23:59Z","timestamp":1761873839000},"page":"10574","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Integrated In Vitro and In Silico Evaluation of the Antimicrobial and Cytotoxic Potential of Calotropis procera Leaf Ethanolic Extract: From GC-MS Profiling to Molecular Docking and Dynamics"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5247-867X","authenticated-orcid":false,"given":"Juan David","family":"Rodr\u00edguez-Mac\u00edas","sequence":"first","affiliation":[{"name":"Facultad de Ciencias de la Salud, Exactas y Naturales, Universidad Libre Seccional Barranquilla, Barranquilla 080001, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4454-3126","authenticated-orcid":false,"given":"Oscar","family":"Saurith-Coronell","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias B\u00e1sicas, Departamento de Qu\u00edmica y Biolog\u00eda, Universidad del Norte, Barranquilla 080003, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Mart\u00ednez Parra","sequence":"additional","affiliation":[{"name":"Estudiante de Maestr\u00eda en Biotecnolog\u00eda, Universidad Libre Seccional Barranquilla, Barranquilla 080001, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domingo C\u00e9sar","family":"Carrascal-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias B\u00e1sicas, Departamento de Qu\u00edmica y Biolog\u00eda, Universidad del Norte, Barranquilla 080003, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0681-0544","authenticated-orcid":false,"given":"Fabio","family":"Fuentes-Gandara","sequence":"additional","affiliation":[{"name":"Department of Natural and Exact Sciences, Universidad de la Costa, Barranquilla 080002, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9662-9505","authenticated-orcid":false,"given":"Daniel","family":"Insuasty","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias B\u00e1sicas, Departamento de Qu\u00edmica y Biolog\u00eda, Universidad del Norte, Barranquilla 080003, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7503-1528","authenticated-orcid":false,"given":"Edgar A.","family":"M\u00e1rquez-Braz\u00f3n","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias B\u00e1sicas, Departamento de Qu\u00edmica y Biolog\u00eda, Universidad del Norte, Barranquilla 080003, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kaur, A., Batish, D.R., Kaur, S., and Chauhan, B.S. (2021). An Overview of the Characteristics and Potential of Calotropis procera From Botanical, Ecological, and Economic Perspectives. Front. Plant Sci., 12.","DOI":"10.3389\/fpls.2021.690806"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S812","DOI":"10.1016\/S2221-1691(12)60318-9","article-title":"Antimicrobial Effect of Calotropis procera Active Principles against Aquatic Microbial Pathogens Isolated from Shrimp and Fishes","volume":"2","author":"Velmurugan","year":"2012","journal-title":"Asian Pac. J. Trop. Biomed."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"14716","DOI":"10.1038\/s41598-023-42086-1","article-title":"Identification of Phytochemical, Antioxidant, Anticancer and Antimicrobial Potential of Calotropis procera Leaf Aqueous Extract","volume":"13","author":"Hojjati","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Saddiq, A.A., Tag, H.M., Doleib, N.M., Salman, A.S., and Hagagy, N. (2022). Antimicrobial, Antigenotoxicity, and Characterization of Calotropis procera and Its Rhizosphere-Inhabiting Actinobacteria: In Vitro and In Vivo Studies. Molecules, 27.","DOI":"10.3390\/molecules27103123"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1954","DOI":"10.1080\/14786419.2016.1266349","article-title":"Chemometric Profile & Antimicrobial Activities of Leaf Extract of Calotropis procera and Calotropis Gigantea","volume":"31","author":"Pattnaik","year":"2017","journal-title":"Nat. Prod. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"16","DOI":"10.36108\/psj\/2202.10.0130","article-title":"Calotropis procera Leaves and Fruits Phytochemical and GCMS Analysis and Evaluation of Their Methanolic Extracts Antimicrobial Effect on Isolated Bacteria","volume":"1","author":"Olu","year":"2022","journal-title":"Plant Sci. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"208","DOI":"10.15835\/nsb12210699","article-title":"Evaluation of Phytochemical Constituents and in Vitro Antimicrobial Activities of Leaves Extracts of Calotropis procera against Certain Human Pathogens","volume":"12","author":"Falana","year":"2020","journal-title":"Not. Sci. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0189-7241(15)30059-X","article-title":"Phytochemical and Antimicrobial Evaluation of Aqueous and Organic Extracts of Calotropis procera Ait Leaf and Latex","volume":"31","author":"Shobowale","year":"2013","journal-title":"Niger. Food J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"103181","DOI":"10.1016\/j.arabjc.2021.103181","article-title":"Important Insights from the Antimicrobial Activity of Calotropis procera","volume":"14","author":"Amini","year":"2021","journal-title":"Arab. J. Chem."},{"key":"ref_10","first-page":"37","article-title":"In-Vitro Studies on Calotropis procera Leaf Extracts as Inhibitors of Key Enzymes Linked to Diabetes Mellitus","volume":"15","author":"Kazeem","year":"2016","journal-title":"Iran. J. Pharm. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"285","DOI":"10.32598\/IJT.16.4.966.1","article-title":"Calotropis procera Root Extract\u2019s Anti-Diabetic and Hepatoprotective Therapeutic Activity in Alloxan-Induced Pancreatic Toxicity in Wistar Rats","volume":"16","author":"Ihegboro","year":"2022","journal-title":"Iran. J. Toxicol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"S230","DOI":"10.1016\/j.arabjc.2011.03.011","article-title":"Phytochemical Investigation of Calotropis procera","volume":"9","author":"Chundattu","year":"2011","journal-title":"Arab. J. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"35854","DOI":"10.1039\/D1RA06703F","article-title":"A Review on Phytochemical Constituents and Pharmacological Potential of Calotropis procera","volume":"11","author":"Wadhwani","year":"2021","journal-title":"RSC Adv."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"175","DOI":"10.20546\/ijcmas.2024.1311.022","article-title":"Antibacterial Activity Investigation and Anti-Biotic Sensitive\u2019s for Different Solvents (Ethanol, Propanol, DMSO and di Ethel Ether) Extracts of Seeds, Leafs and Stems of (Laurus azorica and Avena sterilis) Plants","volume":"13","author":"Aljamal","year":"2024","journal-title":"Int. J. Curr. Microbiol. Appl. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"102173","DOI":"10.1016\/j.jddst.2020.102173","article-title":"Freeze-Dried Crystalline Dispersions: Solid-State, Triboelectrification and Simultaneous Dissolution Improvements","volume":"61","author":"Adebisi","year":"2021","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"112633","DOI":"10.1016\/j.biopha.2022.112633","article-title":"Overcoming Drug Delivery Barriers and Challenges in Topical Therapy of Atopic Dermatitis: A Nanotechnological Perspective","volume":"147","author":"Hemrajani","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1002\/pca.2970","article-title":"TLC\u2013MS Identification of Alkaloids in Leonuri Herba and Leonuri Fructus Aided by a Newly Developed Universal Derivatisation Reagent Optimised by the Response Surface Method","volume":"32","author":"Zhang","year":"2021","journal-title":"Phytochem. Anal."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"126571","DOI":"10.1016\/j.conbuildmat.2022.126571","article-title":"Influence of Tannin and Iron Ions on the Water Resistance of Clay Materials","volume":"323","author":"Du","year":"2022","journal-title":"Constr. Build. Mater."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2166","DOI":"10.1038\/s41598-023-28775-x","article-title":"Extraction and identification of new flavonoid compounds in dandelion Taraxacum mongolicum Hand.-Mazz. with evaluation of antioxidant activities","volume":"13","author":"Wang","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"17543","DOI":"10.1021\/acs.jafc.3c04022","article-title":"The Chemistry Behind the Folin-Ciocalteu Method for the Estimation of (Poly)Phenol Content in Food: Total Phenolic Intake in a Mediterranean Dietary Pattern","volume":"71","year":"2023","journal-title":"J. Agric. Food Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/j.biopha.2016.10.030","article-title":"Plant-Derived Cardiac Glycosides: Role in Heart Ailments and Cancer Management","volume":"84","author":"Patel","year":"2016","journal-title":"Biomed. Pharmacother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"102145","DOI":"10.1016\/j.cis.2020.102145","article-title":"Surface Activity and Foaming Properties of Saponin-Rich Plants Extracts","volume":"279","author":"Wojciechowski","year":"2020","journal-title":"Adv. Colloid Interface Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1046\/j.1365-3032.2003.00329.x","article-title":"Biological Effects of Alkaloids Extracted from Three Plants of Moroccan Arid Areas on the Desert Locust","volume":"28","author":"Abbassi","year":"2003","journal-title":"Physiol. Entomol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1515\/znc-2011-11-1203","article-title":"Antioxidant and Cytotoxic Flavonols from Calotropis procera","volume":"66","author":"Mohamed","year":"2011","journal-title":"Z. Naturforschung Sect. C J. Biosci."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Salih, A.M., Al-Qurainy, F., Nadeem, M., Tarroum, M., Khan, S., Shaikhaldein, H.O., Al-Hashimi, A., Alfagham, A., and Alkahtani, J. (2021). Optimization Method for Phenolic Compounds Extraction from Medicinal Plant (Juniperus procera) and Phytochemicals Screening. Molecules, 26.","DOI":"10.3390\/molecules26247454"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.indcrop.2012.12.043","article-title":"Potential of Using Flavonoids, Latex and Extracts from Calotropis procera (Ait.) as Grain Protectants against Two Coleopteran Pests of Stored Rice","volume":"45","author":"Nenaah","year":"2013","journal-title":"Ind. Crops Prod."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/S0040-4039(01)90578-7","article-title":"The Cardiac Glycosides of Calotropis procera","volume":"4","author":"Crout","year":"1963","journal-title":"Tetrahedron Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.3109\/13880200903490513","article-title":"Extraction and Phytochemical Investigation of Calotropis procera: Effect of Plant Extracts on the Activity of Diverse Muscles","volume":"48","author":"Moustafa","year":"2010","journal-title":"Pharm. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2270","DOI":"10.1093\/jn\/116.11.2270","article-title":"Influence of Saponins on Gut Permeability and Active Nutrient Transport in Vitro","volume":"116","author":"Johnson","year":"1986","journal-title":"J. Nutr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"100535","DOI":"10.1016\/j.aimed.2025.100535","article-title":"Ethnopharmacology of Calotropis procera: Traditional Knowledge and Scientific Insights from Dodoma Region, Tanzania","volume":"12","author":"Nchimbi","year":"2025","journal-title":"Adv. Integr. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e16706","DOI":"10.1016\/j.heliyon.2023.e16706","article-title":"Potential Anticancer Properties of Calotropis procera: An Investigation on Breast and Colon Cancer Cells","volume":"9","author":"Bajbouj","year":"2023","journal-title":"Heliyon"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Tian, X., Gu, L., Zeng, F., Liu, X., Zhou, Y., Dou, Y., Han, J., Zhao, Y., Zhang, Y., and Luo, Q. (2024). Strophanthidin Induces Apoptosis of Human Lung Adenocarcinoma Cells by Promoting TRAIL-DR5 Signaling. Molecules, 29.","DOI":"10.3390\/molecules29040877"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1021\/jm049405a","article-title":"Identification of a Novel Cardenolicle (2\u2032-Oxovoruscharin) from Calotropis procera and the Hemisynthesis of Novel Derivatives Displaying Potent in Vitro Antitumor Activities and High in Vivo Tolerance: Structure-Activity Relationship Analyses","volume":"48","author":"Simon","year":"2005","journal-title":"J. Med. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Rajkovic, J., Novakovic, R., Grujic-Milanovic, J., Ydyrys, A., Ablaikhanova, N., Calina, D., Sharifi-Rad, J., and Al-Omari, B. (2023). An Updated Pharmacological Insight into Calotropin as a Potential Therapeutic Agent in Cancer. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1160616"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Alaimo, A., Ponce, A., Flores-Maldonado, C., and Contreras, R.G. (2025). Cardiac Glycosides: From Natural Defense Molecules to Emerging Therapeutic Agents. Biomolecules, 15.","DOI":"10.3390\/biom15060885"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"112579","DOI":"10.1016\/j.phytochem.2020.112579","article-title":"Lipidomes of Phylogenetically Different Symbiotic Dinoflagellates of Corals","volume":"181","author":"Sikorskaya","year":"2021","journal-title":"Phytochemistry"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"138280","DOI":"10.1016\/j.jhazmat.2025.138280","article-title":"Auxin Inhibited Colonization of Antibiotic Resistant Bacteria in Soybean Sprouts and Spread of Resistance Genes to Endophytic Bacteria: Highlighting Energy Metabolism and Immunity Mechanism","volume":"493","author":"Li","year":"2025","journal-title":"J. Hazard. Mater."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e2100345","DOI":"10.1002\/cbdv.202100345","article-title":"The Influence of Environmental Conditions on Secondary Metabolites in Medicinal Plants: A Literature Review","volume":"18","author":"Pant","year":"2021","journal-title":"Chem. Biodivers."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"106529","DOI":"10.1016\/j.jinf.2025.106529","article-title":"A Benchmarking Study of Thirty-Day Mortality Following Staphylococcus aureus or Escherichia coli Bacteremia","volume":"91","author":"Temkin","year":"2025","journal-title":"J. Infect."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1556\/1886.2019.00021","article-title":"On the Etiological Relevance of Escherichia Coli and Staphylococcus aureus in Superficial and Deep Infections\u2014A Hypothesis-Forming, Retrospective Assessment","volume":"9","author":"Frickmann","year":"2019","journal-title":"Eur. J. Microbiol. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1080\/14760584.2018.1488590","article-title":"Escherichia coli and Staphylococcus aureus: Leading Bacterial Pathogens of Healthcare Associated Infections and Bacteremia in Older-Age Populations","volume":"17","author":"Poolman","year":"2018","journal-title":"Expert Rev. Vaccines"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1128\/CMR.00134-14","article-title":"Staphylococcus aureus Infections: Epidemiology, Pathophysiology, Clinical Manifestations, and Management","volume":"28","author":"Tong","year":"2015","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2449085","DOI":"10.1080\/22221751.2024.2449085","article-title":"Long-Term Impact of Molecular Epidemiology Shifts of Methicillin-Resistant Staphylococcus aureus on Severity and Mortality of Bloodstream Infection","volume":"14","author":"Kaku","year":"2025","journal-title":"Emerg. Microbes Infect."},{"key":"ref_44","first-page":"101","article-title":"Tetracycline Resistance among Escherichia Coli Isolates from Broilers in Iran: A Systematic Review and Meta-Analysis","volume":"54","author":"Hasannejad","year":"2025","journal-title":"Iran. J. Public Health"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"104838","DOI":"10.1016\/j.psj.2025.104838","article-title":"Assessment of Antibiotic Resistance and Virulence in Escherichia Coli Strains Isolated from Poultry in Spain","volume":"104","author":"Monroy","year":"2025","journal-title":"Poult. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Suberviola, B., and Andaluz-Ojeda, D. (2025). Antibiotic Resistance and Mortality in ICU Patients: A Retrospective Analysis of First Culture Growth Results. Antibiotics, 14.","DOI":"10.3390\/antibiotics14030290"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"103659","DOI":"10.1016\/j.sjbs.2023.103659","article-title":"Soluble Laticifer Proteins from Calotropis procera as an Effective Candidates for Antimicrobial Therapeutics","volume":"30","author":"Saher","year":"2023","journal-title":"Saudi J. Biol. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.aoas.2019.12.001","article-title":"Effect of Calotropis procera L. Plant Extract on Seeds Germination and the Growth of Microorganisms","volume":"64","author":"Radwan","year":"2019","journal-title":"Ann. Agric. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"W513","DOI":"10.1093\/nar\/gkae303","article-title":"ProTox 3.0: A Webserver for the Prediction of Toxicity of Chemicals","volume":"52","author":"Banerjee","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Bueno, J. (2020). ADMETox: Bringing Nanotechnology Closer to Lipinski\u2019s Rule of Five, Springer.","DOI":"10.1007\/978-3-030-43855-5_5"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/2052-4374-25-11","article-title":"Hazard Classification of Household Chemical Products in Korea According to the Globally Harmonized System of Classification and Labeling of Chemicals","volume":"25","author":"Kim","year":"2013","journal-title":"Ann. Occup. Environ. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1016\/S1359-6446(04)03297-0","article-title":"Improvingthe Decision-Making Process in Structural Modification of Drug Candidates: Reducing Toxicity","volume":"9","author":"Nassar","year":"2004","journal-title":"Drug Discov. Today"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1080\/17460441.2018.1508207","article-title":"Toxicity Mechanism-Based Prodrugs: Glutathione-Dependent Bioactivation as a Strategy for Anticancer Prodrug Design","volume":"13","author":"Zhang","year":"2018","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Liu, Q., Sun, H., Li, X., Sheng, H., and Zhu, L. (2022). Strategies for Solubility and Bioavailability Enhancement and Toxicity Reduction of Norcantharidin. Molecules, 27.","DOI":"10.3390\/molecules27227740"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"W356","DOI":"10.1093\/nar\/gkx374","article-title":"PharmMapper 2017 Update: A Web Server for Potential Drug Target Identification with a Comprehensive Target Pharmacophore Database","volume":"45","author":"Wang","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3034","DOI":"10.1016\/j.bmc.2018.03.012","article-title":"A Genetically Selected Cyclic Peptide Inhibitor of BCL6 Homodimerization","volume":"26","author":"Osher","year":"2018","journal-title":"Bioorg Med. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"110753","DOI":"10.1016\/j.pnpbp.2023.110753","article-title":"Acute Administration of a Dopamine D2\/D3 Receptor Agonist Alters Behavioral and Neural Parameters in Adult Zebrafish","volume":"125","author":"Nabinger","year":"2023","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"104907","DOI":"10.1016\/j.micpath.2021.104907","article-title":"Type 3 Secretion System as an Anti-Pseudomonal Target","volume":"155","author":"Horna","year":"2021","journal-title":"Microb. Pathog."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"110044","DOI":"10.1016\/j.cclet.2024.110044","article-title":"Application of Inhibitors Targeting the Type III Secretion System in Phytopathogenic Bacteria","volume":"36","author":"He","year":"2025","journal-title":"Chin. Chem. Lett."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1007\/s12088-025-01486-9","article-title":"Targeting Type III Secretion System Using Salmonella: A Promising Candidate for Innovative Antibacterial Therapy","volume":"65","author":"Shreya","year":"2025","journal-title":"Indian J. Microbiol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Zhou, J., Cai, Y., Liu, Y., An, H., Deng, K., Ashraf, M.A., Zou, L., and Wang, J. (2022). Breaking down the Cell Wall: Still an Attractive Antibacterial Strategy. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.952633"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e202414325","DOI":"10.1002\/anie.202414325","article-title":"Fighting Antimicrobial Resistance: Innovative Drugs in Antibacterial Research","volume":"64","author":"Gao","year":"2025","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1038\/s41573-023-00791-6","article-title":"Unrealized Targets in the Discovery of Antibiotics for Gram-Negative Bacterial Infections","volume":"22","author":"Theuretzbacher","year":"2023","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Hirakawa, H., Kurushima, J., Hashimoto, Y., and Tomita, H. (2020). Progress Overview of Bacterial Two-Component Regulatory Systems as Potential Targets for Antimicrobial Chemotherapy. Antibiotics, 9.","DOI":"10.3390\/antibiotics9100635"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/s41368-021-00137-1","article-title":"Molecular Mechanisms of Inhibiting Glucosyltransferases for Biofilm Formation in Streptococcus Mutans","volume":"13","author":"Zhang","year":"2021","journal-title":"Int. J. Oral Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"7098","DOI":"10.1038\/s41598-024-57702-x","article-title":"A Comprehensive Computational Study to Explore Promising Natural Bioactive Compounds Targeting Glycosyltransferase MurG in Escherichia coli for Potential Drug Development","volume":"14","author":"Shtaiwi","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Liu, Y., Huang, Y., Fan, C., Chi, Z., Bai, M., Sun, L., Yang, L., Yu, C., Song, Z., and Yang, X. (2021). Ursolic Acid Targets Glucosyltransferase and Inhibits Its Activity to Prevent Streptococcus Mutans Biofilm Formation. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.743305"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.1094\/PHYTO-11-21-0457-R","article-title":"Multi-Omics Analysis Reveals That the Antimicrobial Kasugamycin Potential Targets Nitrate Reductase in Didymella Segeticola to Achieve Control of Tea Leaf Spot","volume":"112","author":"Jiang","year":"2022","journal-title":"Phytopathology"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1186\/s40001-023-01413-y","article-title":"From Nitrate to NO: Potential Effects of Nitrate-Reducing Bacteria on Systemic Health and Disease","volume":"28","author":"Liu","year":"2023","journal-title":"Eur. J. Med. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1080\/08927014.2024.2446928","article-title":"Inhibition of Salmonella Typhimurium Biofilm and Polysaccharide Production via Eugenol-Glucosyltransferase Interactions","volume":"41","year":"2025","journal-title":"Biofouling"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1039\/D1NP00072A","article-title":"Bioactive Natural Products from Bacteroidetes","volume":"39","author":"Brinkmann","year":"2022","journal-title":"Nat. Prod. Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/mBio.00207-21","article-title":"Nira Is an Alternative Nitrite Reductase from Pseudomonas Aeruginosa with Potential as an Antivirulence Target","volume":"12","author":"Fenn","year":"2021","journal-title":"mBio"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1111\/mmi.14610","article-title":"Mode of Action of Lipoprotein Modification Enzymes\u2014Novel Antibacterial Targets","volume":"115","author":"Legood","year":"2021","journal-title":"Mol. Microbiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.drudis.2016.01.005","article-title":"Compound High-Quality Criteria: A New Vision to Guide the Development of Drugs, Current Situation","volume":"21","author":"Mignani","year":"2016","journal-title":"Drug Discov. Today"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"112244","DOI":"10.1016\/j.jep.2019.112244","article-title":"Botany, Traditional Uses, Phytochemistry and Biological Activities of Cardamom [Elettaria cardamomum (L.) Maton]\u2014A Critical Review","volume":"246","author":"Ashokkumar","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"4625","DOI":"10.1128\/jb.173.15.4625-4636.1991","article-title":"The MurG Gene of Escherichia Coli Codes for the UDP-N-Acetylglucosamine:N-Acetylmuramyl-(Pentapeptide) Pyrophosphoryl-Undecaprenol N-Acetylglucosamine Transferase Involved in the Membrane Steps of Peptidoglycan Synthesis","volume":"173","author":"Texier","year":"1991","journal-title":"J. Bacteriol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1073\/pnas.0235749100","article-title":"Crystal Structure of the MurG:UDP-GlcNAc Complex Reveals Common Structural Principles of a Superfamily of Glycosyltransferases","volume":"100","author":"Hu","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"6824","DOI":"10.1021\/bi0256678","article-title":"Intrinsic Lipid Preferences and Kinetic Mechanism of Escherichia Coli MurG","volume":"41","author":"Chen","year":"2002","journal-title":"Biochemistry"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2442","DOI":"10.1021\/cb400487f","article-title":"Murgocil Is a Highly Bioactive Staphylococcal-Specific Inhibitor of the Peptidoglycan Glycosyltransferase Enzyme MurG","volume":"8","author":"Mann","year":"2013","journal-title":"ACS Chem. Biol."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Liu, Y., and Breukink, E. (2016). The Membrane Steps of Bacterial Cell Wall Synthesis as Antibiotic Targets. Antibiotics, 5.","DOI":"10.3390\/antibiotics5030028"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1126\/science.1063611","article-title":"Genetic Basis for Activity Differences Between Vancomycin and Glycolipid Derivatives of Vancomycin","volume":"294","author":"Eggert","year":"2001","journal-title":"Science"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e202400896","DOI":"10.1002\/cmdc.202400896","article-title":"New Inhibitors of \u03b2-1,4-Galactosyltransferase I Discovered by Virtual Screening","volume":"20","author":"Kranjc","year":"2025","journal-title":"ChemMedChem"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1111\/j.1365-2958.2007.05851.x","article-title":"The Essential Peptidoglycan Glycosyltransferase MurG Forms a Complex with Proteins Involved in Lateral Envelope Growth as Well as with Proteins Involved in Cell Division in Escherichia coli","volume":"65","author":"Mohammadi","year":"2007","journal-title":"Mol. Microbiol."},{"key":"ref_84","unstructured":"Yunta, M.J.R. (2012). Using Molecular Modelling to Study Interactions Between Molecules with Biological Activity. Bioinformatics, Oxford University Press."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s42252-024-00062-6","article-title":"Simulation-Based Assessment of Zwitterionic Pendant Group Variations on the Hemocompatibility of Polyethersulfone Membranes","volume":"5","author":"Nazari","year":"2024","journal-title":"Funct. Compos. Mater."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"6522","DOI":"10.2174\/13816128113199990440","article-title":"Non-Covalent Interactions with Aromatic Rings: Current Understanding and Implications for Rational Drug Design","volume":"19","author":"Li","year":"2013","journal-title":"Curr. Pharm. Des."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1021\/acs.jcim.6b00678","article-title":"Molecular Dynamics in Mixed Solvents Reveals Protein-Ligand Interactions, Improves Docking, and Allows Accurate Binding Free Energy Predictions","volume":"57","author":"Arcon","year":"2017","journal-title":"J. Chem. Inf. Model."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1021\/acs.jcim.2c01444","article-title":"Analysis of Protein Folding Simulation with Moving Root Mean Square Deviation","volume":"63","author":"Maruyama","year":"2023","journal-title":"J. Chem. Inf. Model."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"3088","DOI":"10.1021\/ci300385h","article-title":"Molecular Dynamics Investigation on a Series of HIV Protease Inhibitors: Assessing the Performance of MM-PBSA and MM-GBSA Approaches","volume":"52","author":"Srivastava","year":"2012","journal-title":"J. Chem. Inf. Model."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1517\/17460441.2015.1032936","article-title":"The MM\/PBSA and MM\/GBSA Methods to Estimate Ligand-Binding Affinities","volume":"10","author":"Genheden","year":"2015","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"4574","DOI":"10.1021\/jm060222t","article-title":"Insight through Molecular Mechanics Poisson-Boltzmann Surface Area Calculations into the Binding Affinity of Triclosan and Three Analogues for FabI, the E. Coli Enoyl Reductase","volume":"49","author":"Rafi","year":"2006","journal-title":"J. Med. Chem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1021\/ci100275a","article-title":"Assessing the Performance of the MM\/PBSA and MM\/GBSA Methods. 1. The Accuracy of Binding Free Energy Calculations Based on Molecular Dynamics Simulations","volume":"51","author":"Hou","year":"2011","journal-title":"J. Chem. Inf. Model."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Sierra-Hernandez, O., Saurith-Coronell, O., Rodr\u00edguez-Mac\u00edas, J., M\u00e1rquez, E., Mora, J.R., Paz, J.L., Flores-Sumoza, M., Mendoza-Mendoza, A., Flores-Morales, V., and Marrero-Ponce, Y. (2025). In Silico Identification of Potential Clovibactin-like Antibiotics Binding to Unique Cell Wall Precursors in Diverse Gram-Positive Bacterial Strains. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26041724"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1002\/cphc.202000968","article-title":"On the Effect of the Various Assumptions and Approximations Used in Molecular Simulations on the Properties of Bio-Molecular Systems: Overview and Perspective on Issues","volume":"22","author":"Daura","year":"2021","journal-title":"ChemPhysChem"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"S451","DOI":"10.1098\/rsif.2008.0505.focus","article-title":"Methods for Improving Simulations of Biological Systems: Systemic Computation and Fractal Proteins","volume":"6","author":"Bentley","year":"2009","journal-title":"J. R. Soc. Interface"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.ijpharm.2019.04.058","article-title":"Managing Efficacy and Toxicity of Drugs: Targeted Delivery and Excretion","volume":"565","author":"Kundu","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1177\/0192623309354341","article-title":"Safety Assessment Considerations and Strategies for Targeted Small Molecule Cancer Therapeutics in Drug Discovery","volume":"38","author":"Westhouse","year":"2010","journal-title":"Toxicol. Pathol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1007\/s40333-019-0016-7","article-title":"Mesophyll Thickness and Sclerophylly among Calotropis procera Morphotypes Reveal Water-Saved Adaptation to Environments","volume":"11","author":"Pompelli","year":"2019","journal-title":"J. Arid. Land."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"104819","DOI":"10.1016\/j.jaridenv.2022.104819","article-title":"Range Distribution of the Invasive Alien Species Calotropis procera in South America Dry Environments under Climatic Change Scenarios","volume":"205","author":"Rodrigues","year":"2022","journal-title":"J. Arid. Environ."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"13626","DOI":"10.15835\/nbha52213626","article-title":"Spectral Characterization, Analgesic, and Anti-Inflammatory Effects of Ethanolic Extract of Calotropis procera Leaf and Dry Latex from Jazan, Kingdom of Saudi Arabia","volume":"52","author":"Alam","year":"2024","journal-title":"Not. Bot. Horti Agrobot. Cluj. Napoca"},{"key":"ref_101","first-page":"e60354","article-title":"Calotropis procera and the Pharmacological Properties of Its Aqueous Leaf Extract: A Review","volume":"16","author":"Habeeb","year":"2024","journal-title":"Cureus"},{"key":"ref_102","first-page":"1","article-title":"Phytochemical and Antibacterial Screening of Leaves and Latex of Calotropis procera: A Comparison","volume":"2","author":"Joshi","year":"2024","journal-title":"Univ. J. Phytochem. Ayurvedic Heights"},{"key":"ref_103","first-page":"459","article-title":"Antibacterial Potential and Time-Kill Kinetics of Calotropis procera Extracts","volume":"3","author":"Andrew","year":"2024","journal-title":"UMYU Sci."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Kastrat, E., and Cheng, H.P. (2024). Escherichia Coli Has an Undiscovered Ability to Inhibit the Growth of Both Gram-Negative and Gram-Positive Bacteria. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-57996-x"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.ijantimicag.2018.12.015","article-title":"Formation of Pseudomonas Aeruginosa Inhibition Zone during Tobramycin Disk Diffusion Is Due to Transition from Planktonic to Biofilm Mode of Growth","volume":"53","author":"Henneberg","year":"2019","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Melo, R.S., Azevedo, \u00c1.M.A., Pereira, A.M.G., Rocha, R.R., Cavalcante, R.M.B., Matos, M.N.C., Lopes, P.H.R., Gomes, G.A., Rodrigues, T.H.S., and Dos Santos, H.S. (2019). Chemical Composition and Antimicrobial Effectiveness of Ocimum Gratissimum L. Essential Oil Against Multidrug-Resistant Isolates of Staphylococcus aureus and Escherichia coli. Molecules, 24.","DOI":"10.3390\/molecules24213864"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Chometon, T.Q., Da Silva Siqueira, M., Sant\u2019anna, J.C., Almeida, M.R., Gandini, M., De Almeida Nogueira, A.C.M., and Antas, P.R.Z. (2020). A Protocol for Rapid Monocyte Isolation and Generation of Singular Human Monocyte-Derived Dendritic Cells. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0231132"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1089\/bio.2015.0104","article-title":"Comparison of Three Isolation Techniques for Human Peripheral Blood Mononuclear Cells: Cell Recovery and Viability, Population Composition, and Cell Functionality","volume":"14","author":"Grievink","year":"2016","journal-title":"Biopreserv Biobank"},{"key":"ref_109","first-page":"820","article-title":"Viability Testof Lemongrass Extract (Cymbopogon Citratus) on BHK-21 Fibroblast Cell Culture","volume":"20","author":"Supandi","year":"2020","journal-title":"Med. Leg. Update"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Mu\u00f1oz-Acevedo, A., Gonz\u00e1lez, M.C., De Moya, Y.S., and Rodr\u00edguez, J.D. (2023). Volatile Metabolites of Piper Eriopodon (Miq.) C.DC. from Northern Region of Colombia and Assessment of In Vitro Bioactivities of the Leaf Essential Oil. Molecules, 28.","DOI":"10.3390\/molecules28062594"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1758-2946-2-1","article-title":"Molecular Structure Input on the Web","volume":"2","author":"Ertl","year":"2010","journal-title":"J. Cheminform"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/1758-2946-5-24","article-title":"JSME: A Free Molecule Editor in JavaScript","volume":"5","author":"Bienfait","year":"2013","journal-title":"J. Cheminform"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/1758-2946-3-33","article-title":"Open Babel: An Open Chemical Toolbox","volume":"3","author":"Banck","year":"2011","journal-title":"J. Cheminform"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2462","DOI":"10.1021\/ci6005646","article-title":"Generating Conformer Ensembles Using a Multiobjective Genetic Algorithm","volume":"47","author":"Vainio","year":"2007","journal-title":"J. Chem. Inf. Model."},{"key":"ref_115","first-page":"51","article-title":"ADME Principles in Small Molecule Drug Discovery and Development: An Industrial Perspective","volume":"1","author":"Cannady","year":"2022","journal-title":"Toxicol. Pathol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"180","DOI":"10.54037\/WJPS.2021.91207","article-title":"Role of Drug Metabolism & Disposition in Discovery and Development of New Drugs","volume":"9","author":"Joshi","year":"2021","journal-title":"World J. Pharm. Sci."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1080\/10408347.2022.2066461","article-title":"de B. Advances in Activity\/Property Prediction from Chemical Structures","volume":"54","author":"Saunders","year":"2024","journal-title":"Crit. Rev. Anal. Chem."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"W257","DOI":"10.1093\/nar\/gky318","article-title":"ProTox-II: A Webserver for the Prediction of Toxicity of Chemicals","volume":"46","author":"Banerjee","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1016\/j.drudis.2014.01.006","article-title":"Addressing Toxicity Risk When Designing and Selecting Compounds in Early Drug Discovery","volume":"19","author":"Segall","year":"2014","journal-title":"Drug Discov. Today"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.copbio.2009.08.003","article-title":"Docking and Chemoinformatic Screens for New Ligands and Targets","volume":"20","author":"Kolb","year":"2009","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.4155\/fmc-2016-0143","article-title":"Molecular Docking for Drug Discovery and Development: A Widely Used Approach but Far from Perfect","volume":"8","author":"Wang","year":"2016","journal-title":"Future Med. Chem."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1021\/acs.jctc.0c01006","article-title":"Accelerating A Uto D Ock 4 with GPUs and Gradient-Based Local Search","volume":"17","author":"Tillack","year":"2021","journal-title":"J. Chem. Theory Comput."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"3891","DOI":"10.1021\/acs.jcim.1c00203","article-title":"AutoDock Vina 1.2.0: New Docking Methods, Expanded Force Field, and Python Bindings","volume":"61","author":"Eberhardt","year":"2021","journal-title":"J. Chem. Inf. Model."},{"key":"ref_124","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_125","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1002\/jcc.21256","article-title":"Software News and Updates AutoDock4 and AutoDockTools4: Automated Docking with Selective Receptor Flexibility","volume":"30","author":"Morris","year":"2009","journal-title":"J. Comput. Chem."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Salo-Ahen, O.M.H., Alanko, I., Bhadane, R., Alexandre, A.M., Honorato, R.V., Hossain, S., Juffer, A.H., Kabedev, A., Lahtela-Kakkonen, M., and Larsen, A.S. (2020). Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development. Processes, 9.","DOI":"10.3390\/pr9010071"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1021\/acs.jafc.1c06110","article-title":"Integration of Molecular Docking Analysis and Molecular Dynamics Simulations for Studying Food Proteins and Bioactive Peptides","volume":"70","author":"Liceaga","year":"2022","journal-title":"J. Agric. Food Chem."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/978-1-0716-3441-7_7","article-title":"Applications of Molecular Dynamics Simulations in Drug Discovery","volume":"2714","author":"AlRawashdeh","year":"2024","journal-title":"Methods Mol. Biol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1111\/cbdd.14038","article-title":"Application of Molecular Dynamics Simulation in Biomedicine","volume":"99","author":"Wu","year":"2022","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"239","DOI":"10.22159\/ijap.2021v13i3.41202","article-title":"Virtual Target Construction for Structure-Based Screening in the Discovery of Histamine H2 Receptor Ligands","volume":"13","author":"Nugraha","year":"2021","journal-title":"Int. J. Appl. Pharm."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1021\/acs.jcim.0c01217","article-title":"Binding Thermodynamics and Interaction Patterns of Inhibitor-Major Urinary Protein-I Binding from Extensive Free-Energy Calculations: Benchmarking AMBER Force Fields","volume":"61","author":"Huai","year":"2021","journal-title":"J. Chem. Inf. Model."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"8414","DOI":"10.1021\/acs.jctc.3c00899","article-title":"Is the Functional Response of a Receptor Determined by the Thermodynamics of Ligand Binding?","volume":"19","author":"Zhang","year":"2023","journal-title":"J. Chem. Theory Comput."},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Sapundzhi, F., Popstoilov, M., and Lazarova, M. (2023). RMSD Calculations for Comparing Protein Three-Dimensional Structures. Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics). Numberical Methoda and Applications, Spinger.","DOI":"10.1007\/978-3-031-32412-3_25"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/21\/10574\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T01:31:06Z","timestamp":1761874266000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/21\/10574"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,30]]},"references-count":133,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["ijms262110574"],"URL":"https:\/\/doi.org\/10.3390\/ijms262110574","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,30]]}}}