{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T07:13:41Z","timestamp":1780384421868,"version":"3.54.1"},"reference-count":78,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T00:00:00Z","timestamp":1695945600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>This study explores the potential inhibitory activity of alkaloids, a class of natural compounds isolated from Brazilian biodiversity, against the mJHBP enzyme of the Aedes aegypti mosquito. This mosquito is a significant vector of diseases such as dengue, zika, and chikungunya. The interactions between the ligands and the enzyme at the molecular level were evaluated using computational techniques such as molecular docking, molecular dynamics (MD), and molecular mechanics with generalized Born surface area (MMGBSA) free energy calculation. The findings suggest that these compounds exhibit a high binding affinity with the enzyme, as confirmed by the binding free energies obtained in the simulation. Furthermore, the specific enzyme residues that contribute the most to the stability of the complex with the compounds were identified: specifically, Tyr33, Trp53, Tyr64, and Tyr129. Notably, Tyr129 residues were previously identified as crucial in the enzyme inhibition process. This observation underscores the significance of the research findings and the potential of the evaluated compounds as natural insecticides against Aedes aegypti mosquitoes. These results could stimulate the development of new vector control agents that are more efficient and environmentally friendly.<\/jats:p>","DOI":"10.3390\/molecules28196871","type":"journal-article","created":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T09:39:32Z","timestamp":1695980372000},"page":"6871","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Exploring Natural Alkaloids from Brazilian Biodiversity as Potential Inhibitors of the Aedes aegypti Juvenile Hormone Enzyme: A Computational Approach for Vector Mosquito Control"],"prefix":"10.3390","volume":"28","author":[{"given":"Renato Ara\u00fajo da","family":"Costa","sequence":"first","affiliation":[{"name":"Laboratory of Biosolutions and Bioplastics of the Amazon, Graduate Program in Science and Environment, Institute of Exact and Natural Sciences, Federal University of Par\u00e1 (UFPA), Bel\u00e9m 66075-110, PA, Brazil"},{"name":"Laboratory of Molecular Biology, Evolution and Microbiology, Federal Institute of Education, Science and Technology of Par\u00e1 (IFPA) Campus Abaetetuba, Abaetetuba 68440-000, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9ia do Socorro Silva da","family":"Costa","sequence":"additional","affiliation":[{"name":"Laboratory of Biosolutions and Bioplastics of the Amazon, Graduate Program in Science and Environment, Institute of Exact and Natural Sciences, Federal University of Par\u00e1 (UFPA), Bel\u00e9m 66075-110, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3178-2362","authenticated-orcid":false,"given":"Jo\u00e3o Augusto Pereira da","family":"Rocha","sequence":"additional","affiliation":[{"name":"Graduate Program in Chemistry, Federal University of Par\u00e1 (UFPA), Bel\u00e9m 66075-110, PA, Brazil"},{"name":"Laboratory of Modeling and Computational Chemistry, Federal Institute of Education, Science and Technology of Par\u00e1 (IFPA) Campus Bragan\u00e7a, Bragan\u00e7a 68600-000, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlon Ramires da Costa","family":"Lima","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Evolution and Microbiology, Federal Institute of Education, Science and Technology of Par\u00e1 (IFPA) Campus Abaetetuba, Abaetetuba 68440-000, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine Cristina Medeiros da","family":"Rocha","sequence":"additional","affiliation":[{"name":"Graduate Program in Chemistry, Federal University of Par\u00e1 (UFPA), Bel\u00e9m 66075-110, PA, Brazil"},{"name":"Laboratory of Modeling and Computational Chemistry, Federal Institute of Education, Science and Technology of Par\u00e1 (IFPA) Campus Bragan\u00e7a, Bragan\u00e7a 68600-000, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiana Cristina de Ara\u00fajo","family":"Nascimento","sequence":"additional","affiliation":[{"name":"Laboratory of Biosolutions and Bioplastics of the Amazon, Graduate Program in Science and Environment, Institute of Exact and Natural Sciences, Federal University of Par\u00e1 (UFPA), Bel\u00e9m 66075-110, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anderson Jos\u00e9 Baia","family":"Gomes","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Evolution and Microbiology, Federal Institute of Education, Science and Technology of Par\u00e1 (IFPA) Campus Abaetetuba, Abaetetuba 68440-000, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0891-6438","authenticated-orcid":false,"given":"Jos\u00e9 de Arimat\u00e9ia Rodrigues do","family":"Rego","sequence":"additional","affiliation":[{"name":"Laboratory of Biosolutions and Bioplastics of the Amazon, Graduate Program in Science and Environment, Institute of Exact and Natural Sciences, Federal University of Par\u00e1 (UFPA), Bel\u00e9m 66075-110, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davi do Socorro Barros","family":"Brasil","sequence":"additional","affiliation":[{"name":"Laboratory of Biosolutions and Bioplastics of the Amazon, Graduate Program in Science and Environment, Institute of Exact and Natural Sciences, Federal University of Par\u00e1 (UFPA), Bel\u00e9m 66075-110, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,29]]},"reference":[{"key":"ref_1","unstructured":"(2023, May 18). Vector-Borne Diseases. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/vector-borne-diseases."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1186\/s13071-022-05594-z","article-title":"Discovery of Novel Natural Products for Mosquito Control","volume":"15","author":"Engdahl","year":"2022","journal-title":"Parasites Vectors"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e000530","DOI":"10.1136\/bmjgh-2017-000530","article-title":"Zika, Chikungunya and Dengue: The Causes and Threats of New and Re-Emerging Arboviral Diseases","volume":"3","author":"Teixeira","year":"2018","journal-title":"BMJ Glob. Health"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1038\/s41564-019-0376-y","article-title":"Past and Future Spread of the Arbovirus Vectors Aedes aegypti and Aedes albopictus","volume":"4","author":"Kraemer","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ferreira, Q.R., Lemos, F.F., Moura, M.N., Nascimento, J.O., Novaes, A.F., Barcelos, I.S., Fernandes, L.A., Amaral, L.S., Barreto, F.K., and Melo, F.F. (2023). Role of the Microbiome in Aedes spp. Vector Competence: What Do We Know?. Viruses, 15.","DOI":"10.3390\/v15030779"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Godoy, R.S.M., dos Santos Felix, L., da Silva Orfan\u00f3, A., Chaves, B.A., Nogueira, P.M., dos Anjos Costa, B., Soares, A.S., Oliveira, C.C.A., Nacif-Pimenta, R., and Silva, B.M. (2021). Dengue and Zika Virus Infection Patterns Vary among Aedes aegypti Field Populations from Belo Horizonte, a Brazilian Endemic City. PLoS Negl. Trop. Dis., 15.","DOI":"10.1371\/journal.pntd.0009839"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"12925","DOI":"10.1038\/s41598-020-69759-5","article-title":"Proliferation of Aedes aegypti in Urban Environments Mediated by the Availability of Key Aquatic Habitats","volume":"10","author":"Wilke","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Morrison, A.C., Zielinski-Gutierrez, E., Scott, T.W., and Rosenberg, R. (2008). Defining Challenges and Proposing Solutions for Control of the Virus Vector Aedes aegypti. PLoS Med., 5.","DOI":"10.1371\/journal.pmed.0050068"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"517","DOI":"10.2105\/AJPH.2017.303652","article-title":"Leaking Containers: Success and Failure in Controlling the Mosquito Aedes aegypti in Brazil","volume":"107","year":"2017","journal-title":"Am. J. Public Health"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1186\/s13071-021-04785-4","article-title":"Dengue Fever and Insecticide Resistance in Aedes Mosquitoes in Southeast Asia: A Review","volume":"14","author":"Gan","year":"2021","journal-title":"Parasites Vectors"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"21062","DOI":"10.1038\/s41598-021-00432-1","article-title":"Juvenile Hormone Analog Enhances Zika Virus Infection in Aedes aegypti","volume":"11","author":"Alomar","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Benelli, G., Jeffries, C.L., and Walker, T. (2016). Biological Control of Mosquito Vectors: Past, Present, and Future. Insects, 7.","DOI":"10.3390\/insects7040052"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.actatropica.2009.10.015","article-title":"Resistance to the Organophosphate Temephos: Mechanisms, Evolution and Reversion in an Aedes aegypti Laboratory Strain from Brazil","volume":"113","author":"Gomes","year":"2010","journal-title":"Acta Trop."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1093\/jme\/tjab035","article-title":"Influence of Pyrethroid Resistance on Vector Competency for Zika Virus by Aedes aegypti (Diptera: Culicidae)","volume":"58","author":"Connelly","year":"2021","journal-title":"J. Med. Entomol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.sbspro.2012.03.008","article-title":"Aedes Mosquitoes Resistance in Urban Community Setting","volume":"36","author":"Shafie","year":"2012","journal-title":"Procedia-Soc. Behav. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1007\/s11101-017-9512-6","article-title":"Phytochemical Biopesticides: Some Recent Developments","volume":"16","author":"Walia","year":"2017","journal-title":"Phytochem. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.aspen.2010.03.003","article-title":"Permethrin Resistance in Aedes aegypti (Linnaeus) Collected from Kuala Lumpur, Malaysia","volume":"13","author":"Nazni","year":"2010","journal-title":"J. Asia-Pac. Entomol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1934578X19862893","DOI":"10.1177\/1934578X19862893","article-title":"Larvicidal Activity of Secondary Plant Metabolites in Aedes aegypti Control: An Overview of the Previous 6 Years","volume":"14","year":"2019","journal-title":"Nat. Product. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1055\/a-1320-4610","article-title":"The Potential of Biologically Active Brazilian Plant Species as a Strategy to Search for Molecular Models for Mosquito Control","volume":"87","author":"Valli","year":"2021","journal-title":"Planta Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"610","DOI":"10.3389\/fpls.2017.00610","article-title":"Progress on Azadirachta Indica Based Biopesticides in Replacing Synthetic Toxic Pesticides","volume":"8","author":"Chaudhary","year":"2017","journal-title":"Front. Plant Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"105854","DOI":"10.1016\/j.micpath.2022.105854","article-title":"Plant Based Natural Products as Potential Ecofriendly and Safer Biopesticides: A Comprehensive Overview of Their Advantages over Conventional Pesticides, Limitations and Regulatory Aspects","volume":"173","author":"Khursheed","year":"2022","journal-title":"Microb. Pathog."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"\u015eeng\u00fcl Demirak, M.\u015e., and Canpolat, E. (2022). Plant-Based Bioinsecticides for Mosquito Control: Impact on Insecticide Resistance and Disease Transmission. Insects, 13.","DOI":"10.3390\/insects13020162"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.cropro.2018.04.011","article-title":"Terpene Based Biopesticides as Potential Alternatives to Synthetic Insecticides for Control of Aphid Pests on Protected Ornamentals","volume":"110","author":"Smith","year":"2018","journal-title":"Crop Prot."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1016\/j.biortech.2007.02.023","article-title":"Larvicidal Activity of Saponins from Balanites Aegyptiaca Callus against Aedes aegypti Mosquito","volume":"99","author":"Chapagain","year":"2008","journal-title":"Bioresour. Technol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.jep.2004.10.004","article-title":"A Study of the Larvicidal and Molluscicidal Activities of Some Medicinal Plants from Northeast Brazil","volume":"97","author":"Bieber","year":"2005","journal-title":"J. Ethnopharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"105179","DOI":"10.1016\/j.actatropica.2019.105179","article-title":"Towards the Optimization of Botanical Insecticides Research: Aedes aegypti Larvicidal Natural Products in French Guiana","volume":"201","author":"Falkowski","year":"2020","journal-title":"Acta Trop."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1002\/arch.21012","article-title":"Effect of Moringa Oleifera Flower Extract on Larval Trypsin and Acetylcholinesterase Activities in Aedes aegypti","volume":"79","author":"Pontual","year":"2012","journal-title":"Arch. Insect Biochem. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.cbpc.2008.08.004","article-title":"Larvicidal Activity of Lectins from Myracrodruon Urundeuva on Aedes aegypti","volume":"149","author":"Gomes","year":"2009","journal-title":"Comp. Biochem. Physiol. Part. C Toxicol. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Silv\u00e9rio, M.R.S., Espindola, L.S., Lopes, N.P., and Vieira, P.C. (2020). Plant Natural Products for the Control of Aedes aegypti: The Main Vector of Important Arboviruses. Molecules, 25.","DOI":"10.3390\/molecules25153484"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.aspen.2021.05.011","article-title":"Molecular Docking Studies of Natural Alkaloids as Acetylcholinesterase (AChE1) Inhibitors in Aedes aegypti","volume":"24","author":"Balachandran","year":"2021","journal-title":"J. Asia-Pac. Entomol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6647","DOI":"10.1016\/j.biortech.2009.06.092","article-title":"Larvicidal Activity against Aedes aegypti of Some Plants Native to the West-Central Region of Brazil","volume":"100","author":"Garcez","year":"2009","journal-title":"Bioresour. Technol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1186\/s13071-017-2154-0","article-title":"Larvicidal Activity of Lignans and Alkaloid Identified in Zanthoxylum Piperitum Bark toward Insecticide-Susceptible and Wild Culex Pipiens Pallens and Aedes aegypti","volume":"10","author":"Kim","year":"2017","journal-title":"Parasites Vectors"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1007\/s00436-012-2923-9","article-title":"Mosquito Larvicidal Activity of Alkaloids and Limonoids Derived from Evodia Rutaecarpa Unripe Fruits against Aedes albopictus (Diptera: Culicidae)","volume":"111","author":"Liu","year":"2012","journal-title":"Parasitol. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.sajb.2019.06.020","article-title":"Bioactivity of Couroupita guianensis Aubl. against Filarial and Dengue Vectors and Non-Target Fish","volume":"125","author":"Maheswaran","year":"2019","journal-title":"S. Afr. J. Bot."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1186\/1756-3305-7-312","article-title":"Toxicity of Six Plant Extracts and Two Pyridone Alkaloids from Ricinus communis against the Malaria Vector Anopheles gambiae","volume":"7","author":"Wachira","year":"2014","journal-title":"Parasites Vectors"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1080\/09670874.2021.1917723","article-title":"Recent Advances for Alkaloids as Botanical Pesticides for Use in Organic Agriculture","volume":"69","author":"Wu","year":"2021","journal-title":"Int. J. Pest. Manag."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2360","DOI":"10.1002\/ps.5772","article-title":"Two Novel Alkaloids from Corydalis curviflora Maxim. and Their Insecticidal Activity","volume":"76","author":"Xia","year":"2020","journal-title":"Pest. Manag. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.indcrop.2018.06.082","article-title":"Aphicidal Activities of Amaryllidaceae Alkaloids from Bulbs of Lycoris radiata against Aphis citricola","volume":"123","author":"Yan","year":"2018","journal-title":"Ind. Crops Prod."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Chowa\u0144ski, S., Adamski, Z., Marciniak, P., Rosi\u0144ski, G., B\u00fcy\u00fckg\u00fczel, E., B\u00fcy\u00fckg\u00fczel, K., Falabella, P., Scrano, L., Ventrella, E., and Lelario, F. (2016). A Review of Bioinsecticidal Activity of Solanaceae Alkaloids. Toxins, 8.","DOI":"10.3390\/toxins8030060"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"107811","DOI":"10.1016\/j.compbiolchem.2023.107811","article-title":"Ensemble-Based, High-Throughput Virtual Screening of Potential Inhibitor Targeting Putative Farnesol Dehydrogenase of Metisa plana (Lepidoptera: Psychidae)","volume":"103","author":"Zifruddin","year":"2023","journal-title":"Comput. Biol. Chem."},{"key":"ref_41","unstructured":"Gilbert, L.I. (2012). Insect Endocrinology, Academic Press."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e21615","DOI":"10.1002\/arch.21615","article-title":"The Juvenile Hormone Receptor as a Target of Juvenoid \u201cInsect Growth Regulators\u201d","volume":"103","author":"Jindra","year":"2020","journal-title":"Arch. Insect Biochem. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"104487","DOI":"10.1016\/j.jinsphys.2023.104487","article-title":"Evolution of Proteins Involved in the Final Steps of Juvenile Hormone Synthesis","volume":"145","author":"Smykal","year":"2023","journal-title":"J. Insect Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"15329","DOI":"10.1074\/jbc.M117.802009","article-title":"A Mosquito Hemolymph Odorant-Binding Protein Family Member Specifically Binds Juvenile Hormone","volume":"292","author":"Kim","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"18413","DOI":"10.1038\/s41598-020-75386-x","article-title":"Identification of a Juvenile-Hormone Signaling Inhibitor via High-Throughput Screening of a Chemical Library","volume":"10","author":"Kayukawa","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e2215541119","DOI":"10.1073\/pnas.2215541119","article-title":"Unique Peptidic Agonists of a Juvenile Hormone Receptor with Species-Specific Effects on Insect Development and Reproduction","volume":"119","author":"Tumova","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1021\/ci200269q","article-title":"CSAR Benchmark Exercise of 2010: Combined Evaluation Across All Submitted Scoring Functions","volume":"51","author":"Smith","year":"2011","journal-title":"J. Chem. Inf. Model."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Liu, J., Su, M., Liu, Z., Li, J., Li, Y., and Wang, R. (2017). Enhance the Performance of Current Scoring Functions with the Aid of 3D Protein-Ligand Interaction Fingerprints. BMC Bioinform., 18.","DOI":"10.1186\/s12859-017-1750-5"},{"key":"ref_49","unstructured":"Roy, K. (2019). Silico Drug Design, Academic Press."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/978-1-61779-965-5_6","article-title":"Applications and Limitations of in Silico Models in Drug Discovery","volume":"910","author":"Sacan","year":"2012","journal-title":"Methods Mol. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"12964","DOI":"10.1039\/C6CP01555G","article-title":"Comprehensive Evaluation of Ten Docking Programs on a Diverse Set of Protein\u2013Ligand Complexes: The Prediction Accuracy of Sampling Power and Scoring Power","volume":"18","author":"Wang","year":"2016","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Lima, L.R., Bastos, R.S., Ferreira, E.F.B., Le\u00e3o, R.P., Ara\u00fajo, P.H.F., Pita, S.S.D.R., De Freitas, H.F., Espejo-Rom\u00e1n, J.M., Dos Santos, E.L.V.S., and Ramos, R.D.S. (2022). Identification of Potential New Aedes aegypti Juvenile Hormone Inhibitors from N-Acyl Piperidine Derivatives: A Bioinformatics Approach. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23179927"},{"key":"ref_53","first-page":"101178","article-title":"In Silico Identification and Study of Potential Anti-Mosquito Juvenile Hormone Binding Protein (MJHBP) Compounds as Candidates for Dengue Virus\u2014Vector Insecticides","volume":"28","author":"Ononamadu","year":"2021","journal-title":"Biochem. Biophys. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"da Silva Ramos, R., da Silva Costa, J., Campos Silva, R., Vilhena da Costa, G., Bruno Lobato Rodrigues, A., de Menezes Rabelo, \u00c9., Nonato Pican\u00e7o Souto, R., Anthony Taft, C., Tomich de Paula da Silva, C.H., and Campos Rosa, J.M. (2019). Identification of Potential Inhibitors from Pyriproxyfen with Insecticidal Activity by Virtual Screening. Pharmaceuticals, 12.","DOI":"10.3390\/ph12010020"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4687","DOI":"10.1080\/07391102.2019.1688192","article-title":"Potential Inhibitors of the Enzyme Acetylcholinesterase and Juvenile Hormone with Insecticidal Activity: Study of the Binding Mode via Docking and Molecular Dynamics Simulations","volume":"38","author":"Ramos","year":"2020","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_56","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_57","doi-asserted-by":"crossref","unstructured":"da Costa, R.A., da Rocha, J.A.P., Pinheiro, A.S., da Costa, A.D.S.S., da Rocha, E.C.M., Silva, R.C., Gon\u00e7alves, A.D.S., Santos, C.B.R., and Brasil, D.D.S.B. (2022). A Computational Approach Applied to the Study of Potential Allosteric Inhibitors Protease NS2B\/NS3 from Dengue Virus. Molecules, 27.","DOI":"10.3390\/molecules27134118"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1134\/S0026893308040195","article-title":"Radius of Gyration as an Indicator of Protein Structure Compactness","volume":"42","author":"Lobanov","year":"2008","journal-title":"Mol. Biol."},{"key":"ref_59","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_60","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1007\/s00044-018-2280-z","article-title":"Studies of NMR, Molecular Docking, and Molecular Dynamics Simulation of New Promising Inhibitors of Cruzaine from the Parasite Trypanosoma Cruzi","volume":"28","author":"Costa","year":"2019","journal-title":"Med. Chem. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1128\/AAC.05292-11","article-title":"Molecular Dynamics Approaches Estimate the Binding Energy of HIV-1 Integrase Inhibitors and Correlate with In Vitro Activity","volume":"56","author":"Johnson","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"W537","DOI":"10.1093\/nar\/gks375","article-title":"H++ 3.0: Automating pK prediction and the preparation of biomolecular structures for atomistic molecular modeling and simulations","volume":"40","author":"Anandakrishnan","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1006\/jmbi.1996.0897","article-title":"Development and Validation of a Genetic Algorithm for Flexible Docking","volume":"267","author":"Jones","year":"1997","journal-title":"J. Mol. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1002\/prot.10465","article-title":"Improved Protein-Ligand Docking Using GOLD","volume":"52","author":"Verdonk","year":"2003","journal-title":"Proteins"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1021\/ci800298z","article-title":"Empirical Scoring Functions for Advanced Protein\u2212Ligand Docking with PLANTS","volume":"49","author":"Korb","year":"2009","journal-title":"J. Chem. Inf. Model."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"7215","DOI":"10.1038\/s41598-017-07451-x","article-title":"NuBBEDB: An Updated Database to Uncover Chemical and Biological Information from Brazilian Biodiversity","volume":"7","author":"Pilon","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1021\/np3006875","article-title":"Development of a Natural Products Database from the Biodiversity of Brazil","volume":"76","author":"Valli","year":"2013","journal-title":"J. Nat. Prod."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1021\/acs.jcim.8b00462","article-title":"GPU-Accelerated Molecular Dynamics and Free Energy Methods in Amber18: Performance Enhancements and New Features","volume":"58","author":"Lee","year":"2018","journal-title":"J. Chem. Inf. Model."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3696","DOI":"10.1021\/acs.jctc.5b00255","article-title":"Ff14SB: Improving the Accuracy of Protein Side Chain and Backbone Parameters from Ff99SB","volume":"11","author":"Maier","year":"2015","journal-title":"J. Chem. Theory Comput."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1002\/jcc.20035","article-title":"Development and Testing of a General Amber Force Field","volume":"25","author":"Wang","year":"2004","journal-title":"J. Comput. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"10096","DOI":"10.1063\/1.1808117","article-title":"A Modified TIP3P Water Potential for Simulation with Ewald Summation","volume":"121","author":"Price","year":"2004","journal-title":"J. Chem. Phys."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/0021-9991(77)90098-5","article-title":"Numerical Integration of the Cartesian Equations of Motion of a System with Constraints: Molecular Dynamics of n-Alkanes","volume":"23","author":"Ryckaert","year":"1977","journal-title":"J. Comput. Phys."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"693","DOI":"10.2298\/JSC210929011D","article-title":"In Silico Identification of Novel Allosteric Inhibitors of Dengue Virus NS2B\/NS3 Serine Protease: Scientific Paper","volume":"87","author":"Pinheiro","year":"2022","journal-title":"J. Serbian Chem. Soc."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"10089","DOI":"10.1063\/1.464397","article-title":"Particle Mesh Ewald: An N\u00b7log(N) Method for Ewald Sums in Large Systems","volume":"98","author":"Darden","year":"1993","journal-title":"J. Chem. Phys."},{"key":"ref_75","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":"Wang","year":"2019","journal-title":"Chem. Rev."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3314","DOI":"10.1021\/ct300418h","article-title":"MMPBSA.Py: An Efficient Program for End-State Free Energy Calculations","volume":"8","author":"Miller","year":"2012","journal-title":"J. Chem. Theory Comput."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1021\/ar000033j","article-title":"Calculating Structures and Free Energies of Complex Molecules:\u2009 Combining Molecular Mechanics and Continuum Models","volume":"33","author":"Kollman","year":"2000","journal-title":"Acc. Chem. Res."},{"key":"ref_78","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."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/19\/6871\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:02:08Z","timestamp":1760130128000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/19\/6871"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,29]]},"references-count":78,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["molecules28196871"],"URL":"https:\/\/doi.org\/10.3390\/molecules28196871","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,29]]}}}