{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T02:24:11Z","timestamp":1771727051066,"version":"3.50.1"},"reference-count":62,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T00:00:00Z","timestamp":1739750400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T00:00:00Z","timestamp":1739750400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100006565","name":"University of Johannesburg","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006565","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Comput Aided Mol Des"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The COVID-19 pandemic, caused by SARS-CoV-2, has underscored the urgent need for effective antiviral therapies, particularly against vaccine-resistant variants. This study investigates natural xanthone derivatives as potential inhibitors of the ACE2 receptor, a critical entry point for the virus. We computationally evaluated 91 xanthone compounds derived from\n                    <jats:italic>Swertia chirayita<\/jats:italic>\n                    , identifying two promising candidates: 8-O-[\u03b2-D-Xylopyranosyl-(1\u21926)-\u03b2-D-glucopyranosyl]-1,7-dihydroxy-3-methoxy xanthone (XAN71) and 8-O-[\u03b2-D-Xylopyranosyl-(1\u21926)-\u03b2-D-glucopyranosyl]-1-hydroxy-3,7-dimethoxy-xanthone (XAN72). Molecular docking and dynamics simulations (MDDS) were performed to assess their binding energy and stability within the ACE2 active site, comparing them to the reference inhibitor MLN-4067. The top six compounds were selected based on their docking performance, followed by Molecular Mechanics\/Poisson-Boltzmann Surface Area (MM\/PBSA) calculations to quantify binding affinities. Additionally, molecular electrostatic potential (MEP) analysis was conducted to visualize electron density regions relevant to binding interactions. Our results demonstrate that XAN71 and XAN72 exhibit superior binding affinities of -70.97 and \u2212\u200969.85\u00a0kcal\/mol, respectively, outperforming MLN-4067 (-61.33\u00a0kcal\/mol). MD simulations revealed stable interactions with key ACE2 residues, primarily through hydrogen bonds and hydrophobic contacts. The Molecular Electrostatic Potential(MEP) analysis further elucidated critical electron density regions that enhance binding stability. This study establishes XAN71 and XAN72 as viable candidates for ACE2 inhibition, providing a structural basis for their development as natural xanthone-based therapeutics against SARS-CoV-2. These findings highlight the potential of targeting ACE2 with natural compounds to combat COVID-19, particularly in light of emerging viral variants.\n                  <\/jats:p>","DOI":"10.1007\/s10822-025-00585-5","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T06:51:52Z","timestamp":1739775112000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["In silico exploration of natural xanthone derivatives as potential inhibitors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication and cellular entry"],"prefix":"10.1007","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6151-7009","authenticated-orcid":false,"given":"Vincent A.","family":"Obakachi","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8337-9260","authenticated-orcid":false,"given":"Vaderament-A.","family":"Nchiozem-Ngnitedem","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3079-5989","authenticated-orcid":false,"given":"Krishna K.","family":"Govender","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3011-6675","authenticated-orcid":false,"given":"Penny P.","family":"Govender","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2025,2,17]]},"reference":[{"key":"585_CR1","doi-asserted-by":"crossref","unstructured":"Miyah Y, Benjelloun M, Lairini S, Lahrichi A (2022) COVID-19 impact on public health, environment, human psychology, global Socioeconomy, and education, The Scientific World Journal, vol. no. 1, p. 5578284","DOI":"10.1155\/2022\/5578284"},{"key":"585_CR2","unstructured":"WHO (2024) COVID-19 cases, (World Health Organization) WHO COVID-19 dashboard, https:\/\/data.who.int\/dashboards\/covid19\/cases"},{"key":"585_CR3","doi-asserted-by":"crossref","unstructured":"Ameratunga R et al (2024) SARS-CoV-2 evolution has increased resistance to monoclonal antibodies and first-generation COVID-19 vaccines: is there a future therapeutic role for soluble ACE2 receptors for COVID-19? Antiviral Res, vol. 227, p. 105894","DOI":"10.1016\/j.antiviral.2024.105894"},{"key":"585_CR4","doi-asserted-by":"crossref","unstructured":"Oriola AO, Kar P (2024) Naturally Occurring Xanthones and Their Biological Implications, Molecules, vol. 29, no. 17, p. 4241","DOI":"10.3390\/molecules29174241"},{"key":"585_CR5","doi-asserted-by":"crossref","unstructured":"Suhandi C, Alfathonah SS, Hasanah AN (2023) Potency of xanthone derivatives from Garcinia mangostana L. for COVID-19 treatment through angiotensin-converting Enzyme 2 and main protease blockade: a computational study, Molecules, vol. 28, no. 13, p. 5187","DOI":"10.3390\/molecules28135187"},{"issue":"1","key":"585_CR6","first-page":"443","volume":"4","author":"SO OLALEKAN","year":"2023","unstructured":"Olalekan SO, Adeyanju MM, Osonuga IO, Babatunde T (2023) Human SARS CoV-2 spike protein mutations in West Africa. Health Sci Investigations J 4(1):443\u2013447","journal-title":"Health Sci Investigations J"},{"key":"585_CR7","doi-asserted-by":"crossref","unstructured":"Zhou P et al (2020) A pneumonia outbreak associated with a new coronavirus of probable bat origin, nature, vol. 579, no. 7798, pp. 270\u2013273","DOI":"10.1038\/s41586-020-2012-7"},{"issue":"11","key":"585_CR8","doi-asserted-by":"publisher","first-page":"3688","DOI":"10.1016\/j.bmcl.2012.04.028","volume":"22","author":"TT Dao","year":"2012","unstructured":"Dao TT, Dang TT, Nguyen PH, Kim E, Thuong PT, Oh WK (2012) Xanthones from Polygala karensium inhibit neuraminidases from influenza A viruses. Bioorg Med Chem Lett 22(11):3688\u20133692","journal-title":"Bioorg Med Chem Lett"},{"key":"585_CR9","doi-asserted-by":"crossref","unstructured":"Wu Y-P et al (2013) Three novel xanthones from Garcinia paucinervis and their anti-TMV activity, Molecules, vol. 18, no. 8, pp. 9663\u20139669","DOI":"10.3390\/molecules18089663"},{"issue":"4","key":"585_CR10","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.1021\/np500124e","volume":"77","author":"H Zhang","year":"2014","unstructured":"Zhang H et al (2014) Prenylated benzoylphloroglucinols and xanthones from the leaves of Garcinia Oblongifolia with antienteroviral activity. J Nat Prod 77(4):1037\u20131046","journal-title":"J Nat Prod"},{"issue":"11","key":"585_CR11","doi-asserted-by":"publisher","first-page":"449","DOI":"10.3390\/md16110449","volume":"16","author":"H-H Kang","year":"2018","unstructured":"Kang H-H et al (2018) Potential antiviral xanthones from a coastal saline soil fungus aspergillus iizukae. Mar Drugs 16(11):449","journal-title":"Mar Drugs"},{"key":"585_CR12","doi-asserted-by":"publisher","first-page":"105968","DOI":"10.1016\/j.antiviral.2024.105968","volume":"229","author":"EH Oliveira","year":"2024","unstructured":"Oliveira EH et al (2024) A mimetic peptide of ACE2 protects against SARS-CoV-2 infection and decreases pulmonary inflammation related to COVID-19. Antiviral Res 229:105968","journal-title":"Antiviral Res"},{"issue":"5","key":"585_CR13","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1021\/np020518b","volume":"66","author":"A Abdel-Lateff","year":"2003","unstructured":"Abdel-Lateff A, Klemke C, K\u00f6nig GM, Wright AD (2003) Two new xanthone derivatives from the algicolous marine fungus wardomyces anomalus. J Nat Prod 66(5):706\u2013708. https:\/\/doi.org\/10.1021\/np020518b","journal-title":"J Nat Prod"},{"issue":"7","key":"585_CR14","doi-asserted-by":"publisher","first-page":"2236","DOI":"10.1016\/j.bmc.2014.02.014","volume":"22","author":"WM Abdel-Mageed","year":"2014","unstructured":"Abdel-Mageed WM et al (2014) Benzophenone C-glucosides and gallotannins from mango tree stem bark with broad-spectrum anti-viral activity. Bioorg Med Chem 22(7):2236\u20132243","journal-title":"Bioorg Med Chem"},{"issue":"1","key":"585_CR15","first-page":"6106959","volume":"2017","author":"GC Brand\u00e3o","year":"2017","unstructured":"Brand\u00e3o GC, Kroon EG, Souza Filho JD, Oliveira AB (2017) Antiviral activity of Fridericia Formosa (Bureau) LG Lohmann (Bignoniaceae) extracts and constituents. J Trop Med 2017(1):6106959","journal-title":"J Trop Med"},{"issue":"11","key":"585_CR16","doi-asserted-by":"publisher","first-page":"1537","DOI":"10.1021\/np000175m","volume":"63","author":"A Groweiss","year":"2000","unstructured":"Groweiss A, Cardellina JH, Boyd MR (2000) HIV-Inhibitory Prenylated xanthones and flavones from Maclura t inctoria. J Nat Prod 63(11):1537\u20131539","journal-title":"J Nat Prod"},{"key":"585_CR17","doi-asserted-by":"crossref","unstructured":"Liu F-a et al (1999) Xanthones and quinolones derivatives produced by the deep-sea-derived fungus Penicillium sp. SCSIO Ind16F01, Molecules, vol. 22, no. 12, p. 2017","DOI":"10.3390\/molecules22121999"},{"key":"585_CR18","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.fitote.2019.03.031","volume":"135","author":"N Liu","year":"2019","unstructured":"Liu N et al (2019) Structurally diverse sesquiterpenoids and polyketides from a sponge-associated fungus aspergillus sydowii SCSIO41301. Fitoterapia 135:27\u201332","journal-title":"Fitoterapia"},{"issue":"2","key":"585_CR19","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1038\/ja.2014.97","volume":"68","author":"C Qin","year":"2015","unstructured":"Qin C et al (2015) Sesquiterpenoids and xanthones derivatives produced by sponge-derived fungus stachybotry sp. HH1 ZSDS1F1-2. J Antibiot 68(2):121\u2013125","journal-title":"J Antibiot"},{"issue":"4","key":"585_CR20","doi-asserted-by":"publisher","first-page":"115304","DOI":"10.1016\/j.bmc.2020.115304","volume":"28","author":"DZ Rechenchoski","year":"2020","unstructured":"Rechenchoski DZ et al (2020) Mangiferin: a promising natural xanthone from Mangifera indica for the control of acyclovir\u2013resistant herpes simplex virus 1 infection. Bioorg Med Chem 28(4):115304","journal-title":"Bioorg Med Chem"},{"key":"585_CR21","doi-asserted-by":"crossref","unstructured":"Reutrakul V et al (2007) Cytotoxic and anti-HIV-1 caged xanthones from the resin and fruits of Garcinia hanburyi, Planta medica, vol. 73, no. 01, pp. 33\u201340","DOI":"10.1055\/s-2006-951748"},{"issue":"1","key":"585_CR22","doi-asserted-by":"publisher","first-page":"17796","DOI":"10.1038\/s41598-022-22668-1","volume":"12","author":"AR Issahaku","year":"2022","unstructured":"Issahaku AR et al (2022) Characterization of the binding of MRTX1133 as an avenue for the discovery of potential KRASG12D inhibitors for cancer therapy. Sci Rep 12(1):17796","journal-title":"Sci Rep"},{"issue":"1","key":"585_CR23","doi-asserted-by":"publisher","first-page":"8656","DOI":"10.1038\/s41598-023-35161-0","volume":"13","author":"M Rudrapal","year":"2023","unstructured":"Rudrapal M et al (2023) Dual synergistic inhibition of COX and LOX by potential chemicals from Indian daily spices investigated through detailed computational studies. Sci Rep 13(1):8656","journal-title":"Sci Rep"},{"key":"585_CR24","doi-asserted-by":"crossref","unstructured":"Issahaku AR et al (2023) Discovery of potential KRAS-SOS1 inhibitors from South African natural compounds: an in silico approach, ChemistrySelect, vol. 8, no. 24, p. e202300277","DOI":"10.1002\/slct.202300277"},{"key":"585_CR25","doi-asserted-by":"crossref","unstructured":"Lan J et al (2020) Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor, nature, vol. 581, no. 7807, pp. 215\u2013220","DOI":"10.1038\/s41586-020-2180-5"},{"issue":"6485","key":"585_CR26","doi-asserted-by":"publisher","first-page":"1444","DOI":"10.1126\/science.abb2762","volume":"367","author":"R Yan","year":"2020","unstructured":"Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q (2020) Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science 367(6485):1444\u20131448","journal-title":"Science"},{"issue":"17","key":"585_CR27","doi-asserted-by":"publisher","first-page":"17996","DOI":"10.1074\/jbc.M311191200","volume":"279","author":"P Towler","year":"2004","unstructured":"Towler P et al (2004) ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis. J Biol Chem 279(17):17996\u201318007","journal-title":"J Biol Chem"},{"key":"585_CR28","unstructured":"Schr\u00f6dinger LG, Schr\u00f6dinger Suite 2023-2. New, York NY (2023) Available from: https:\/\/www.schrodinger.com\/platform\/products\/glide\/"},{"key":"585_CR29","doi-asserted-by":"crossref","unstructured":"Papageorgiou AC, Mohsin I (2020) The SARS-CoV-2 spike glycoprotein as a drug and vaccine target: structural insights into its complexes with ACE2 and antibodies, Cells, vol. 9, no. 11, p. 2343","DOI":"10.3390\/cells9112343"},{"key":"585_CR30","doi-asserted-by":"crossref","unstructured":"Frisch M (2016) Gaussian 16. Revision B, 1","DOI":"10.1007\/978-3-658-13361-0_47-1"},{"key":"585_CR31","doi-asserted-by":"crossref","unstructured":"Matondo A et al (2022) In silico drug repurposing of anticancer drug 5-FU and analogues against SARS-CoV-2 main protease: molecular docking, molecular dynamics simulation, pharmacokinetics and chemical reactivity studies. Adv Appl Bioinf Chem, vol. 15, pp. 59\u201377","DOI":"10.2147\/AABC.S366111"},{"key":"585_CR32","volume-title":"AMBER 20","author":"D Case","year":"2020","unstructured":"Case D et al (2020) AMBER 20. University of California, San Francisco"},{"issue":"8","key":"585_CR33","doi-asserted-by":"publisher","first-page":"3696","DOI":"10.1021\/acs.jctc.5b00255","volume":"11","author":"JA Maier","year":"2015","unstructured":"Maier JA, Martinez C, Kasavajhala K, Wickstrom L, Hauser KE, Simmerling C (2015) ff14SB: improving the accuracy of protein side chain and backbone parameters from ff99SB. J Chem Theory Comput 11(8):3696\u20133713","journal-title":"J Chem Theory Comput"},{"key":"585_CR34","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40203-014-0004-8","volume":"2","author":"PC Nair","year":"2014","unstructured":"Nair PC, Miners JO (2014) Molecular dynamics simulations: from structure function relationships to drug discovery. silico Pharmacol 2:1\u20134","journal-title":"silico Pharmacol"},{"issue":"9","key":"585_CR35","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1002\/jcc.20035","volume":"25","author":"J Wang","year":"2004","unstructured":"Wang J, Wolf RM, Caldwell JW, Kollman PA, Case DA (2004) Development and testing of a general amber force field. J Comput Chem 25(9):1157\u20131174","journal-title":"J Comput Chem"},{"issue":"5","key":"585_CR36","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1002\/bip.360320508","volume":"32","author":"RJ Loncharich","year":"1992","unstructured":"Loncharich RJ, Brooks BR, Pastor RW (1992) Langevin dynamics of peptides: the frictional dependence of isomerization rates of N-acetylalanyl\u2010N\u2032\u2010methylamide. Biopolymers: Original Res Biomolecules 32(5):523\u2013535","journal-title":"Biopolymers: Original Res Biomolecules"},{"issue":"1","key":"585_CR37","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1140\/epjst\/e2011-01525-9","volume":"200","author":"R Elber","year":"2011","unstructured":"Elber R, Ruymgaart AP, Hess B (2011) SHAKE parallelization. Eur Phys J Special Top 200(1):211\u2013223","journal-title":"Eur Phys J Special Top"},{"issue":"5","key":"585_CR38","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.1021\/ci500161d","volume":"54","author":"E Seifert","year":"2014","unstructured":"Seifert E (2014) OriginPro 9.1: scientific data analysis and graphing software-software review. J Chem Inf Model 54(5):1552","journal-title":"J Chem Inf Model"},{"issue":"16","key":"585_CR39","doi-asserted-by":"publisher","first-page":"1999","DOI":"10.1002\/jcc.10349","volume":"24","author":"Y Duan","year":"2003","unstructured":"Duan Y et al (2003) A point-charge force field for molecular mechanics simulations of proteins based on condensed\u2010phase quantum mechanical calculations. J Comput Chem 24(16):1999\u20132012","journal-title":"J Comput Chem"},{"issue":"3","key":"585_CR40","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1016\/S0006-3495(97)78756-3","volume":"72","author":"MK Gilson","year":"1997","unstructured":"Gilson MK, Given JA, Bush BL, McCammon JA (1997) The statistical-thermodynamic basis for computation of binding affinities: a critical review. Biophys J 72(3):1047\u20131069","journal-title":"Biophys J"},{"issue":"8","key":"585_CR41","doi-asserted-by":"publisher","first-page":"e0268269","DOI":"10.1371\/journal.pone.0268269","volume":"17","author":"AJ Owoloye","year":"2022","unstructured":"Owoloye AJ et al (2022) Molecular docking, simulation and binding free energy analysis of small molecules as pf HT1 inhibitors. PLoS ONE 17(8):e0268269","journal-title":"PLoS ONE"},{"key":"585_CR42","doi-asserted-by":"crossref","unstructured":"Kuzemsky, A. L. (2015), Variational principle of Bogoliubov and generalized mean fields in many-particle interacting systems. Int J Mod Phys B, Vol. 18, p. 1530010","DOI":"10.1142\/S0217979215300108"},{"key":"585_CR43","doi-asserted-by":"crossref","unstructured":"Adejoro I, Akintemi E, Adeboye O, Ibeji C (2014) Quantum mechanical studies of the structure-activity relationship and electronic vibration of some dietary flavonoids, Asian Journal of Applied Sciences, Vol. 7, No. 3, p. 117\u2013128","DOI":"10.3923\/ajaps.2014.117.128"},{"issue":"1","key":"585_CR44","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s13065-025-01380-x","volume":"19","author":"LK Zuma","year":"2025","unstructured":"Zuma LK et al (2025) Assessing the efficacy of iso-mukaadial acetate and betulinic acid against selected Plasmodium Falciparum glycolytic pathway proteins: in silico and in vitro studies. BMC Chem 19(1):16","journal-title":"BMC Chem"},{"key":"585_CR45","doi-asserted-by":"publisher","first-page":"108906","DOI":"10.1016\/j.jmgm.2024.108906","volume":"134","author":"QM Thai","year":"2025","unstructured":"Thai QM et al (2025) Estimating AChE inhibitors from MCE database by machine learning and atomistic calculations. J Mol Graph Model 134:108906","journal-title":"J Mol Graph Model"},{"key":"585_CR46","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1007\/s12551-016-0247-1","volume":"9","author":"NS Pagadala","year":"2017","unstructured":"Pagadala NS, Syed K, Tuszynski J (2017) Software for molecular docking: a review. Biophys Rev 9:91\u2013102","journal-title":"Biophys Rev"},{"issue":"8","key":"585_CR47","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1080\/08927022.2022.2045016","volume":"48","author":"VA Obakachi","year":"2022","unstructured":"Obakachi VA et al (2022) Structural based investigation of novel pyrazole-thiazole hybrids as dual CDK-1 and CDK-2 inhibitors for cancer chemotherapy. Mol Simul 48(8):687\u2013701","journal-title":"Mol Simul"},{"key":"585_CR48","doi-asserted-by":"publisher","first-page":"139734","DOI":"10.1016\/j.molstruc.2024.139734","volume":"1320","author":"SD Oladipo","year":"2025","unstructured":"Oladipo SD, Luckay RC, Badeji AA, Zamisa SZ, Olalekan SO, Oladoye PO (2025) Structural studies, DFT computational analysis and inhibitory potential of (E)-N\u2019-(2-bromophenyl)-N-(2, 6-diisopropylphenyl) formamidine against CDK1 and CDK2. J Mol Struct 1320:139734","journal-title":"J Mol Struct"},{"key":"585_CR49","doi-asserted-by":"crossref","unstructured":"Hollingsworth SA, Dror RO (2018) Molecular dynamics simulation for all, Neuron, vol. 99, no. 6, pp. 1129\u20131143","DOI":"10.1016\/j.neuron.2018.08.011"},{"issue":"9","key":"585_CR50","doi-asserted-by":"publisher","first-page":"3314","DOI":"10.1021\/ct300418h","volume":"8","author":"BR Miller III","year":"2012","unstructured":"Miller BR III, McGee TD Jr, Swails JM, Homeyer N, Gohlke H, Roitberg AE (2012) MMPBSA. Py: an efficient program for end-state free energy calculations. J Chem Theory Comput 8(9):3314\u20133321","journal-title":"J Chem Theory Comput"},{"issue":"10","key":"585_CR51","doi-asserted-by":"publisher","first-page":"2626","DOI":"10.1021\/ci4002475","volume":"53","author":"M Ylilauri","year":"2013","unstructured":"Ylilauri M, Pentik\u00e4inen OT (2013) MMGBSA as a tool to understand the binding affinities of filamin\u2013peptide interactions. J Chem Inf Model 53(10):2626\u20132633","journal-title":"J Chem Inf Model"},{"issue":"23","key":"585_CR52","doi-asserted-by":"publisher","first-page":"6118","DOI":"10.1021\/acs.jcim.2c00961","volume":"62","author":"J Chen","year":"2022","unstructured":"Chen J, Zeng Q, Wang W, Sun H, Hu G (2022) Decoding the identification mechanism of an SAM-III riboswitch on ligands through multiple independent gaussian-accelerated molecular dynamics simulations. J Chem Inf Model 62(23):6118\u20136132","journal-title":"J Chem Inf Model"},{"issue":"41","key":"585_CR53","doi-asserted-by":"publisher","first-page":"28479","DOI":"10.1039\/D3CP03392A","volume":"25","author":"J Sun","year":"2023","unstructured":"Sun J, Liu X, Zhang S, Li M, Zhang Q, Chen J (2023) Molecular insights and optimization strategies for the competitive binding of engineered ACE2 proteins: a multiple replica molecular dynamics study. Phys Chem Chem Phys 25(41):28479\u201328496","journal-title":"Phys Chem Chem Phys"},{"key":"585_CR54","unstructured":"Adekunle YA et al (2024) Oleanolic acid purified from the stem bark of Olax Subscorpioidea Oliv. Inhibits the function and catalysis of human 17 \u03b2-hydroxysteroid dehydrogenase 1. J Biomol Struct Dynamics, pp. 1\u201314"},{"key":"585_CR55","doi-asserted-by":"crossref","unstructured":"Kayamba F et al (2024) A promising class of Antiprotozoal agents, design and synthesis of novel pyrimidine\u2013cinnamoyl hybrids. Eur J Med Chem, vol. 281, p. 116944","DOI":"10.1016\/j.ejmech.2024.116944"},{"issue":"17","key":"585_CR56","doi-asserted-by":"publisher","first-page":"11278","DOI":"10.1039\/D3RA01145C","volume":"13","author":"H Nassar","year":"2023","unstructured":"Nassar H, Sippl W, Dahab RA, Taha M (2023) Molecular docking, molecular dynamics simulations and in vitro screening reveal cefixime and ceftriaxone as GSK3\u03b2 covalent inhibitors. RSC Adv 13(17):11278\u201311290","journal-title":"RSC Adv"},{"issue":"1","key":"585_CR57","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1146\/annurev.biophys.30.1.211","volume":"30","author":"W Wang","year":"2001","unstructured":"Wang W, Donini O, Reyes CM, Kollman PA (2001) Biomolecular simulations: recent developments in force fields, simulations of enzyme catalysis, protein-ligand, protein-protein, and protein-nucleic acid noncovalent interactions. Annu Rev BioPhys BioMol Struct 30(1):211\u2013243","journal-title":"Annu Rev BioPhys BioMol Struct"},{"key":"585_CR58","doi-asserted-by":"crossref","unstructured":"Oladipo SD et al (2024) Antidiabetes and antioxidant potential of Schiff bases derived from 2-naphthaldehye and substituted aromatic amines: Synthesis, crystal structure, Hirshfeld surface analysis, computational, and invitro studies, Heliyon, vol. 10, no. 1","DOI":"10.1016\/j.heliyon.2023.e23174"},{"issue":"4","key":"585_CR59","doi-asserted-by":"publisher","first-page":"2189","DOI":"10.1021\/acs.jcim.0c00057","volume":"60","author":"H Guterres","year":"2020","unstructured":"Guterres H, Im W (2020) Improving protein-ligand docking results with high-throughput molecular dynamics simulations. J Chem Inf Model 60(4):2189\u20132198","journal-title":"J Chem Inf Model"},{"key":"585_CR60","doi-asserted-by":"publisher","first-page":"130665","DOI":"10.1016\/j.molstruc.2021.130665","volume":"1241","author":"VA Obakachi","year":"2021","unstructured":"Obakachi VA et al (2021) Design and synthesis of pyrazolone-based compounds as potent blockers of SARS-CoV-2 viral entry into the host cells. J Mol Struct 1241:130665","journal-title":"J Mol Struct"},{"issue":"2","key":"585_CR61","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1007\/s40203-024-00250-z","volume":"12","author":"SO Olalekan","year":"2024","unstructured":"Olalekan SO et al (2024) Exploring the therapeutic potential of prolinamides as multi-targeted agents for Alzheimer\u2019s disease treatment: molecular docking and molecular dynamic simulation studies. Silico Pharmacol 12(2):80","journal-title":"Silico Pharmacol"},{"key":"585_CR62","doi-asserted-by":"publisher","first-page":"137359","DOI":"10.1016\/j.molstruc.2023.137359","volume":"1302","author":"SR Merugu","year":"2024","unstructured":"Merugu SR et al (2024) Novel 4, 5-dibromo-N-phenyl-1H-pyrrole-2-carboxamide hybrids as promising DNA gyrase inhibitors: design, synthesis and antimicrobial evaluation. J Mol Struct 1302:137359","journal-title":"J Mol Struct"}],"container-title":["Journal of Computer-Aided Molecular Design"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10822-025-00585-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10822-025-00585-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10822-025-00585-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T17:56:49Z","timestamp":1762451809000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10822-025-00585-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,17]]},"references-count":62,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["585"],"URL":"https:\/\/doi.org\/10.1007\/s10822-025-00585-5","relation":{},"ISSN":["0920-654X","1573-4951"],"issn-type":[{"value":"0920-654X","type":"print"},{"value":"1573-4951","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,17]]},"assertion":[{"value":"18 December 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 February 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 February 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"7"}}