{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T06:08:08Z","timestamp":1785737288647,"version":"3.56.0"},"reference-count":54,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,8,31]],"date-time":"2022-08-31T00:00:00Z","timestamp":1661904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deanship of Scientific Research at Umm Al-Qura University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Malaria is one of the most important infectious diseases worldwide. The causative of the most severe forms of malaria, Plasmodium falciparum, has developed resistances against all the available antimalarial drugs. In the present study, the phytochemical investigation of the green seaweed Halimeda macroloba has afforded two new compounds 1\u20132, along with 4 known ones 3\u20136. The structures of the compounds had been confirmed using 1&amp; 2D-NMR and HRESIMS analyses. Extensive machine-learning-supported virtual-screening suggested cytochrome-C enzyme as a potential target for compound 2. Docking, absolute-binding-free-energy (\u0394Gbinding) and molecular-dynamics-simulation (MDS) of compound 2 revealed the strong binding interaction of this compound with cytochrome-C. In vitro testing for crude extract and isolated compounds revealed the potential in vitro inhibitory activity of both extract and compound 2 against P. falciparum. The crude extract was able to inhibit the parasite growth with an IC50 value of 1.8 \u00b1 0.35 \u00b5g\/mL. Compound 2 also showed good inhibitory activity with an IC50 value of 3.2 \u00b1 0.23 \u00b5g\/mL. Meanwhile, compound 6 showed moderate inhibitory activity with an IC50 value of 19.3 \u00b1 0.51 \u00b5g\/mL. Accordingly, the scaffold of compound 2 can be considered as a good lead compound for the future development of new antimalarial agents.<\/jats:p>","DOI":"10.3390\/molecules27175617","type":"journal-article","created":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T01:50:51Z","timestamp":1661997051000},"page":"5617","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["New Halogenated Compounds from Halimeda macroloba Seaweed with Potential Inhibitory Activity against Malaria"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4619-343X","authenticated-orcid":false,"given":"Abeer H.","family":"Elmaidomy","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5517-082X","authenticated-orcid":false,"given":"Eman Maher","family":"Zahran","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Deraya University, 7 Universities Zone, New Minia 61111, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3211-4630","authenticated-orcid":false,"given":"Raya","family":"Soltane","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, Adham University College, Umm Al-Qura University, Makkah 21955, Saudi Arabia"},{"name":"Department of Biology, Faculty of Sciences, Tunis El Manar University, Tunis 1068, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahlam","family":"Alasiri","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, Adham University College, Umm Al-Qura University, Makkah 21955, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3466-6551","authenticated-orcid":false,"given":"Hani","family":"Saber","sequence":"additional","affiliation":[{"name":"Department of Botany and Microbiology, Faculty of Science, South Valley University, Qena 83523, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Che Julius","family":"Ngwa","sequence":"additional","affiliation":[{"name":"Division of Cellular and Applied Infection Biology, Institute of Zoology, RWTH Aachen University, 52056 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2264-5558","authenticated-orcid":false,"given":"Gabriele","family":"Pradel","sequence":"additional","affiliation":[{"name":"Division of Cellular and Applied Infection Biology, Institute of Zoology, RWTH Aachen University, 52056 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7267-9636","authenticated-orcid":false,"given":"Faisal","family":"Alsenani","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, College of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1442-183X","authenticated-orcid":false,"given":"Ahmed M.","family":"Sayed","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Nahda University, Beni-Suef 62513, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1014-6922","authenticated-orcid":false,"given":"Usama Ramadan","family":"Abdelmohsen","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Deraya University, 7 Universities Zone, New Minia 61111, Egypt"},{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia 61519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.2147\/IJN.S298900","article-title":"New acaciin-loaded self-assembled nanofibers as mpro inhibitors against bcv as a surrogate model for SARS-CoV-2","volume":"16","author":"Mohamad","year":"2021","journal-title":"Int. J. Nanomed."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Alhadrami, H.A., Thissera, B., Hassan, M.H., Behery, F.A., Ngwa, C.J., Hassan, H.M., Pradel, G., Abdelmohsen, U.R., and Rateb, M.E. (2021). Bio-Guided Isolation of Antimalarial Metabolites from the Coculture of Two Red Sea Sponge-Derived Actinokineospora and Rhodococcus spp. Mar. Drugs, 19.","DOI":"10.3390\/md19020109"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.2174\/1389557518666180305163151","article-title":"Potential anti-malarial agents from endophytic fungi: A review","volume":"18","author":"Ibrahim","year":"2018","journal-title":"Mini-Rev. Med. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e30","DOI":"10.1016\/S1473-3099(16)30323-1","article-title":"Potential of marine natural products against drug-resistant fungal, viral, and parasitic infections","volume":"17","author":"Abdelmohsen","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Osei, E., Kwain, S., Mawuli, G.T., Anang, A.K., Owusu, K.B.-A., Camas, M., Camas, A.S., Ohashi, M., Alexandru-Crivac, C.-N., and Deng, H. (2018). Paenidigyamycin A, potent antiparasitic imidazole alkaloid from the Ghanaian Paenibacillus sp. DE2SH. Mar. Drugs, 17.","DOI":"10.3390\/md17010009"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1021\/acs.jnatprod.7b00876","article-title":"Isolation, derivative synthesis, and structure\u2013activity relationships of antiparasitic bromopyrrole alkaloids from the marine sponge Tedania brasiliensis","volume":"81","author":"Parra","year":"2018","journal-title":"J. Nat. Prod."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Kurimoto, S.-i., Ohno, T., Hokari, R., Ishiyama, A., Iwatsuki, M., \u014cmura, S., Kobayashi, J.i., and Kubota, T. (2018). Ceratinadins E and F, new bromotyrosine alkaloids from an Okinawan marine sponge Pseudoceratina sp. Mar. Drugs, 16.","DOI":"10.3390\/md16120463"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1021\/acs.jnatprod.9b00933","article-title":"Orthoscuticellines A\u2013E, \u03b2-Carboline Alkaloids from the Bryozoan Orthoscuticella ventricosa Collected in Australia","volume":"83","author":"Kleks","year":"2020","journal-title":"J. Nat. Prod."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Smyrniotopoulos, V., Merten, C., Kaiser, M., and Tasdemir, D. (2017). Bifurcatriol, a new antiprotozoal acyclic diterpene from the brown alga Bifurcaria bifurcata. Mar. Drugs, 15.","DOI":"10.3390\/md15080245"},{"key":"ref_10","first-page":"397","article-title":"Antimalarial activity of the isolates from the marine sponge Hyrtios erectus against the chloroquine-resistant Dd2 strain of Plasmodium falciparum","volume":"73","author":"Ju","year":"2018","journal-title":"Z. Nat. C"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Qin, G.-F., Tang, X.-L., Sun, Y.-T., Luo, X.-C., Zhang, J., Van Ofwegen, L., Sung, P.-J., Li, P.-L., and Li, G.-Q. (2018). Terpenoids from the soft coral Sinularia sp. collected in Yongxing Island. Mar. Drugs, 16.","DOI":"10.3390\/md16040127"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2545","DOI":"10.1021\/acs.jnatprod.8b00643","article-title":"Hoshinoamides A and B, acyclic lipopeptides from the marine cyanobacterium Caldora penicillata","volume":"81","author":"Iwasaki","year":"2018","journal-title":"J. Nat. Prod."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Sweeney-Jones, A.M., Gagaring, K., Antonova-Koch, J., Zhou, H., Mojib, N., Soapi, K., Skolnick, J., McNamara, C.W., and Kubanek, J. (2020). Antimalarial peptide and polyketide natural products from the Fijian marine cyanobacterium Moorea producens. Mar. Drugs, 18.","DOI":"10.3390\/md18030167"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Keller, L., Siqueira-Neto, J.L., Souza, J.M., Eribez, K., LaMonte, G.M., Smith, J.E., and Gerwick, W.H. (2020). Palstimolide A: A complex polyhydroxy macrolide with antiparasitic activity. Molecules, 25.","DOI":"10.3390\/molecules25071604"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1021\/acs.jnatprod.7b00917","article-title":"Bastimolide B, an antimalarial 24-membered marine macrolide possessing a tert-butyl group","volume":"81","author":"Shao","year":"2018","journal-title":"J. Nat. Prod."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1080\/10286020.2017.1342636","article-title":"Isolation and structure elucidation of halymeniaol, a new antimalarial sterol derivative from the red alga Halymenia floresii","volume":"20","author":"Meesala","year":"2018","journal-title":"J. Asian Nat. Prod. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1080\/14786419.2019.1611815","article-title":"A new antiplasmodial sterol from Indonesian marine sponge, Xestospongia sp","volume":"35","author":"Murtihapsari","year":"2021","journal-title":"Nat. Prod. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"36042","DOI":"10.1039\/D1RA07103C","article-title":"Identifying the specific-targeted marine cerebrosides against SARS-CoV-2: An integrated computational approach","volume":"11","author":"Zahran","year":"2021","journal-title":"RSC Adv."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Zahran, E.M., Albohy, A., Khalil, A., Ibrahim, A.H., Ahmed, H.A., El-Hossary, E.M., Bringmann, G., and Abdelmohsen, U.R. (2020). Bioactivity potential of marine natural products from Scleractinia-associated microbes and in silico anti-SARS-CoV-2 evaluation. Mar. Drugs, 18.","DOI":"10.3390\/md18120645"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0065-2881(08)60303-X","article-title":"Ecology and taxonomy of Halimeda: Primary producer of coral reefs","volume":"Volume 17","year":"1980","journal-title":"Advances in Marine Biology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.5530\/pj.2020.12.141","article-title":"Green Algae Halimeda macroloba in Spermonde Archipelago: Phytochemical and In Vitro Antibacterial Studies","volume":"12","author":"Latifah","year":"2020","journal-title":"Pharmacogn. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.sajb.2019.08.006","article-title":"New insecticides and antimicrobials derived from Sargassum wightii and Halimeda gracillis seaweeds: Toxicity against mosquito vectors and antibiofilm activity against microbial pathogens","volume":"125","author":"Suganya","year":"2019","journal-title":"S. Afr. J. Bot."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Orfali, R., Rateb, M.E., Hassan, H.M., Alonazi, M., Gomaa, M.R., Mahrous, N., GabAllah, M., Kandeil, A., Perveen, S., and Abdelmohsen, U.R. (2021). Sinapic acid suppresses SARS-CoV-2 replication by targeting its envelope protein. Antibiotics, 10.","DOI":"10.3390\/antibiotics10040420"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1021\/np100374b","article-title":"Topsentinols, 24-isopropyl steroids from the marine sponge Topsentia sp","volume":"73","author":"Dai","year":"2010","journal-title":"J. Nat. Prod."},{"key":"ref_25","unstructured":"Handley, J.T. (2003). Studies of the Secondary Metabolite Content of Tasmanian Caulerpa Species. [Ph.D. Thesis, University of Tasmania]."},{"key":"ref_26","first-page":"263","article-title":"Di-(2-ethylhexyl) Phthalate, a major bioactive metabolite with antimicrobial and cytotoxic activity isolated from River Nile derived fungus Aspergillus awamori","volume":"7","author":"Lotfy","year":"2018","journal-title":"Beni-Suef Univ. J. Basic Appl. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e64547","DOI":"10.1371\/annotation\/1dc83f26-8045-4b63-8a86-24c7b71a7f79","article-title":"Correction: Promising Aedes aegypti Repellent Chemotypes Identified through Integrated QSAR, Virtual Screening, Synthesis, and Bioassay","volume":"9","author":"Oliferenko","year":"2014","journal-title":"PLoS ONE"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1021\/ja00867a053","article-title":"Optically Active Amines. I. N-Isopropylidene Derivatives of Optically Active Open Chain Primary Amines and Their Rotatory Powers","volume":"84","author":"Smith","year":"1962","journal-title":"J. Am. Chem. Soc."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1021\/np049965c","article-title":"Chemical investigation of predator-deterred macroalgae from the Antarctic Peninsula","volume":"67","author":"Ankisetty","year":"2004","journal-title":"J. Nat. Prod."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1007\/s10593-014-1496-1","article-title":"Prediction of the biological activity spectra of organic compounds using the PASS online web resource","volume":"50","author":"Filimonov","year":"2014","journal-title":"Chem. Heterocycl. Compd."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1017\/S0031182004005888","article-title":"The multiple roles of the mitochondrion of the malarial parasite","volume":"129","author":"Krungkrai","year":"2004","journal-title":"Parasitology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/S0169-4758(99)01492-1","article-title":"Malaria Drug Trials\u2013An Ethical Dilemma?","volume":"15","author":"Charlwood","year":"1999","journal-title":"Parasitol. Today"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3245","DOI":"10.1016\/j.ejmech.2010.04.011","article-title":"Quinolines and structurally related heterocycles as antimalarials","volume":"45","author":"Kaur","year":"2010","journal-title":"Eur. J. Med. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"40284","DOI":"10.1039\/D0RA07352K","article-title":"Assessing potential inhibitors of SARS-CoV-2 main protease from available drugs using free energy perturbation simulations","volume":"10","author":"Ngo","year":"2020","journal-title":"RSC Adv."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.5530\/pj.2019.11.228","article-title":"Antimalarial Activity of Microalgae Extracts Based on Inhibition of PfMQO, a Mitochondrial Plasmodium falciparum Enzyme","volume":"11","author":"Endang","year":"2019","journal-title":"Pharmacogn. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1186\/s12936-020-03280-y","article-title":"In silico analysis for factors affecting anti-malarial penetration into red blood cells","volume":"19","author":"Pornputtapong","year":"2020","journal-title":"Malar. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"113084","DOI":"10.1016\/j.ejmech.2020.113084","article-title":"Antimalarial application of quinones: A recent update","volume":"210","author":"Patel","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2770","DOI":"10.1038\/s41598-021-82201-8","article-title":"A metabolomic approach to target antimalarial metabolites in the Artemisia annua fungal endophytes","volume":"11","author":"Alhadrami","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_39","unstructured":"Stahl, E. (1965). Thin-Layer Chromatography, Springer. A Laboratory Handbook."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Alzarea, S.I., Elmaidomy, A.H., Saber, H., Musa, A., Al-Sanea, M.M., Mostafa, E.M., Hendawy, O.M., Youssif, K.A., Alanazi, A.S., and Alharbi, M. (2021). Potential anticancer lipoxygenase inhibitors from the red sea-derived brown algae sargassum cinereum: An in-silico-supported In-Vitro Study. Antibiotics, 10.","DOI":"10.3390\/antibiotics10040416"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Elmaidomy, A.H., Alhadrami, H.A., Amin, E., Aly, H.F., Othman, A.M., Rateb, M.E., Hetta, M.H., Abdelmohsen, U.R., and Hassan, H.M. (2020). Anti-inflammatory and antioxidant activities of terpene-and polyphenol-rich Premna odorata leaves on alcohol-inflamed female wistar albino rat liver. Molecules, 25.","DOI":"10.3390\/molecules25143116"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"11769","DOI":"10.1039\/D2RA01340A","article-title":"The anti-Alzheimer potential of Tamarindus indica: An in vivo investigation supported by in vitro and in silico approaches","volume":"12","author":"Elmaidomy","year":"2022","journal-title":"RSC Adv."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Al-Warhi, T., Zahran, E.M., Selim, S., Al-Sanea, M.M., Ghoneim, M.M., Maher, S.A., Mostafa, Y.A., Alsenani, F., Elrehany, M.A., and Almuhayawi, M.S. (2022). Antioxidant and Wound Healing Potential of Vitis vinifera Seeds Supported by Phytochemical Characterization and Docking Studies. Antioxidants, 11.","DOI":"10.3390\/antiox11050881"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.1002\/ptr.5882","article-title":"Acylated iridoids and rhamnopyranoses from premna odorata (lamiaceae) as novel mesenchymal\u2013epithelial transition factor receptor inhibitors for the control of breast cancer","volume":"31","author":"Elmaidomy","year":"2017","journal-title":"Phytother. Res."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Alnusaire, T.S., Sayed, A.M., Elmaidomy, A.H., Al-Sanea, M.M., Albogami, S., Albqmi, M., Alowaiesh, B.F., Mostafa, E.M., Musa, A., and Youssif, K.A. (2021). An In Vitro and In Silico Study of the Enhanced Antiproliferative and Pro-Oxidant Potential of Olea europaea L. cv. Arbosana Leaf Extract via Elastic Nanovesicles (Spanlastics). Antioxidants, 10.","DOI":"10.3390\/antiox10121860"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1038\/s42256-021-00335-w","article-title":"A machine learning platform to estimate anti-SARS-CoV-2 activities","volume":"3","author":"Kc","year":"2021","journal-title":"Nat. Mach. Intell."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4062","DOI":"10.1080\/07391102.2020.1852964","article-title":"Multitarget in silico studies of Ocimum menthiifolium, family Lamiaceae against SARS-CoV-2 supported by molecular dynamics simulation","volume":"40","author":"Albohy","year":"2022","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1093\/bioinformatics\/16.8.747","article-title":"PASS: Prediction of activity spectra for biologically active substances","volume":"16","author":"Lagunin","year":"2000","journal-title":"Bioinformatics"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s10822-010-9352-6","article-title":"Ligand docking and binding site analysis with PyMOL and Autodock\/Vina","volume":"24","author":"Seeliger","year":"2010","journal-title":"J. Comput. Aided Mol. Des."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Bowers, K.J., Chow, D.E., Xu, H., Dror, R.O., Eastwood, M.P., Gregersen, B.A., Klepeis, J.L., Kolossvary, I., Moraes, M.A., and Sacerdoti, F.D. (2006, January 11\u201317). Scalable algorithms for molecular dynamics simulations on commodity clusters. Proceedings of the SC\u201906: Proceedings of the 2006 ACM\/IEEE Conference on Supercomputing, Tampa, FL, USA.","DOI":"10.1145\/1188455.1188544"},{"key":"ref_51","unstructured":"Release, S. (2017). 3: Desmond Molecular Dynamics System, DE Shaw Research, New York, NY, 2017, Maestro-Desmond Interoperability Tools, Schr\u00f6dinger."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1002\/jcc.20289","article-title":"Scalable molecular dynamics with NAMD","volume":"26","author":"Phillips","year":"2005","journal-title":"J. Comput. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"7207","DOI":"10.1021\/acs.jctc.0c00884","article-title":"CHARMM-GUI free energy calculator for absolute and relative ligand solvation and binding free energy simulations","volume":"16","author":"Kim","year":"2020","journal-title":"J. Chem. Theory Comput."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2302","DOI":"10.1021\/acs.jcim.1c00159","article-title":"Benchmark of Popular Free Energy Approaches Revealing the Inhibitors Binding to SARS-CoV-2 Mpro","volume":"61","author":"Ngo","year":"2021","journal-title":"J. Chem. Inf. Model."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/17\/5617\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:21:02Z","timestamp":1760142062000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/17\/5617"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,31]]},"references-count":54,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["molecules27175617"],"URL":"https:\/\/doi.org\/10.3390\/molecules27175617","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,31]]}}}