{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:03:58Z","timestamp":1789016638497,"version":"build-2803163510"},"reference-count":53,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T00:00:00Z","timestamp":1775260800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deanship of Scientific Research, Vice Presidency for Graduate Studies and Scientific Research, King Faisal University, Saudi Arabia","award":["KFU261260"],"award-info":[{"award-number":["KFU261260"]}]},{"award":["KFU261260"],"award-info":[{"award-number":["KFU261260"]}],"id":[{"id":"https:\/\/ror.org\/00dn43547","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Centro de Investigaci\u00f3n, Universidad Anahuac Quer\u00e9taro"},{"id":[{"id":"https:\/\/ror.org\/000mgxg22","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) represents an escalating global neuropharmacological crisis, with prevalence in high-growth demographic regions such as India projected to exceed 14 million by 2040. This study addresses the urgent need for high-potency, dual-site acetylcholinesterase (AChE) inhibitors through an integrated computational pipeline. We address the failure of mono-target paradigms by designing scaffolds capable of simultaneously anchoring the Catalytic Active Site (CAS) and the Peripheral Anionic Site (PAS). A robust GA-MLR QSAR model was developed from 115 quinoline analogs using 11,135 descriptors. Lead candidates were prioritized via cavity directed molecular docking (7XN1) and 100 ns molecular dynamics (MD) simulations. The five-descriptor model (R2 = 0.7569, QLOO2 = 0.7244) was validated by an external set of 8 experimental compounds (Rext2 = 0.8620). Lead Compound 19 emerged as a superior candidate (\u0394G = \u221211.1 kcal\/mol), exhibiting a stable MD trajectory (PL-RMSD \u2248 2.4 \u00c5) and preserving essential Gly121-His447 catalytic anti-correlations. This study provides a statistically validated scaffold and computational mechanistic foundation for future in vitro experimental validation, advancing the high throughput screening of neuroprotective agents on a global scale.<\/jats:p>","DOI":"10.3390\/ijms27073286","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T02:06:21Z","timestamp":1775441181000},"page":"3286","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Dual-Site Acetylcholinesterase Inhibition and Multiscale Stability of Fused Quinoline Sulfonamides: A Chemoinformatic GA-MLR and Molecular Dynamics Study"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5794-9191","authenticated-orcid":false,"given":"Shrikant S.","family":"Nilewar","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Maliba Pharmacy College, Uka Tarsadia University, Bardoli 394350, Gujarat, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apurva D.","family":"Chavan","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Science, Sandip University, Nashik 422213, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankita R.","family":"Pradhan","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Science, Sandip University, Nashik 422213, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anshuman A.","family":"Tripathy","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Science, Sandip University, Nashik 422213, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2059-4849","authenticated-orcid":false,"given":"Nagaraju","family":"Bandaru","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Sree Dattha Institute of Pharmacy Sheriguda, Ibrahimpatnam, Hyderabad 501510, Telangana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6007-5747","authenticated-orcid":false,"given":"Prashik B.","family":"Dudhe","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Science, Sandip University, Nashik 422213, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1202-535X","authenticated-orcid":false,"given":"Perli Kranti","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis, J.K.K. Nattraja College of Pharmacy, Kumarapalayam 638183, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7783-6485","authenticated-orcid":false,"given":"Sandesh","family":"Lodha","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Maliba Pharmacy College, Uka Tarsadia University, Bardoli 394350, Gujarat, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3328-3559","authenticated-orcid":false,"given":"Ghazala","family":"Muteeb","sequence":"additional","affiliation":[{"name":"Department of Nursing, College of Applied Medical Sciences, King Faisal University, Al-Ahsa 31982, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Peredo-Valderrama","sequence":"additional","affiliation":[{"name":"Ingenier\u00eda en Sistemas Computacionales, Universidad Polit\u00e9cnica de Quer\u00e9taro, Carretera Estatal 420 S\/N, El Rosario, Santiago de Quer\u00e9taro 76240, Quer\u00e9taro, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio Jose","family":"Naranjo-Redondo","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Ingenier\u00eda, Universidad An\u00e1huac Quer\u00e9taro, Circuito Universidades I, Fracci\u00f3n 2 S\/N, Zibat\u00e1, El Marqu\u00e9s 76246, Quer\u00e9taro, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0753-9538","authenticated-orcid":false,"given":"Tushar Janardan","family":"Pawar","sequence":"additional","affiliation":[{"name":"Ingenier\u00eda en Sistemas Computacionales, Universidad Polit\u00e9cnica de Quer\u00e9taro, Carretera Estatal 420 S\/N, El Rosario, Santiago de Quer\u00e9taro 76240, Quer\u00e9taro, Mexico"},{"name":"Centro de Investigaci\u00f3n, Universidad An\u00e1huac Quer\u00e9taro, Circuito Universidades I, Fracci\u00f3n 2 S\/N, Zibat\u00e1, El Marqu\u00e9s 76246, Quer\u00e9taro, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e12385","DOI":"10.1002\/trc2.12385","article-title":"Alzheimer\u2019s disease drug development pipeline: 2023","volume":"9","author":"Cummings","year":"2023","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Xiaopeng, Z., Jing, Y., Xia, L., Xingsheng, W., Juan, D., Yan, L., and Baoshan, L. (2025). Global Burden of Alzheimer\u2019s disease and other dementias in adults aged 65 years and older, 1991\u20132021: Population-based study. Front. Public Health, 13.","DOI":"10.3389\/fpubh.2025.1585711"},{"key":"ref_3","unstructured":"World Population Review (2026, February 03). Alzheimer\u2019s Rates by Country 2026. Available online: https:\/\/worldpopulationreview.com\/country-rankings\/alzheimers-rates-by-country."},{"key":"ref_4","unstructured":"Alzheimer\u2019s Disease International (2026, February 03). Dementia Statistics. Available online: https:\/\/www.alzint.org\/about\/dementia-facts-figures\/dementia-statistics\/."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Yiannopoulou, K.G., Anastasiou, A.I., Zachariou, V., and Pelidou, S.-H. (2019). Reasons for Failed Trials of Disease-Modifying Treatments for Alzheimer Disease and Their Contribution in Recent Research. Biomedicines, 7.","DOI":"10.20944\/preprints201909.0270.v1"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Kong, L., Yang, X., and Xu, J. (2025). Comparison of safety of lecanemab and aducanumab: A real-world disproportionality analysis using the FDA adverse event reporting system. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1593989"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4414","DOI":"10.1093\/brain\/awad188","article-title":"Amyloid-related imaging abnormalities (ARIA): Radiological, biological and clinical characteristics","volume":"146","author":"Hampel","year":"2023","journal-title":"Brain"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"10709","DOI":"10.1038\/s41598-021-90108-7","article-title":"A pharmacovigilance study of association between proton pump inhibitor and dementia event based on FDA adverse event reporting system data","volume":"11","author":"Wu","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"44212","DOI":"10.1038\/s41598-025-32012-y","article-title":"Design, synthesis, and multi-target evaluation of 4-phenyl quinoline-8-sulfonate thiosemicarbazones as potential anti-Alzheimer agents","volume":"15","author":"Saeed","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Grabowska, W., Bijak, M., Szelenberger, R., Gorniak, L., Podogrocki, M., Harmata, P., and Cichon, N. (2025). Acetylcholinesterase as a Multifunctional Target in Amyloid-Driven Neurodegeneration: From Dual-Site Inhibitors to Anti-Agregation Strategies. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26178726"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.1038\/s41598-017-03088-y","article-title":"Gorge Motions of Acetylcholinesterase Revealed by Microsecond Molecular Dynamics Simulations","volume":"7","author":"Cheng","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"30356","DOI":"10.1038\/s41598-024-81285-2","article-title":"Identification of AChE targeted therapeutic compounds for Alzheimer\u2019s disease: An in-silico study with DFT integration","volume":"14","author":"Rawat","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"108352","DOI":"10.1016\/j.neuropharm.2020.108352","article-title":"Efficacy of acetylcholinesterase inhibitors in Alzheimer\u2019s disease","volume":"190","author":"Marucci","year":"2021","journal-title":"Neuropharmacology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"21826","DOI":"10.1038\/srep21826","article-title":"Discovery of novel PDE9 inhibitors capable of inhibiting A\u03b2 aggregation as potential candidates for the treatment of Alzheimer\u2019s disease","volume":"6","author":"Su","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/s41392-023-01484-7","article-title":"Amyloid \u03b2-based therapy for Alzheimer\u2019s disease: Challenges, successes and future","volume":"8","author":"Zhang","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5481","DOI":"10.1038\/s41380-021-01249-0","article-title":"The Amyloid-\u03b2 Pathway in Alzheimer\u2019s Disease","volume":"26","author":"Hampel","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"16485","DOI":"10.1074\/jbc.R116.714576","article-title":"Cross-interactions between the Alzheimer Disease Amyloid-\u03b2 Peptide and Other Amyloid Proteins: A Further Aspect of the Amyloid Cascade Hypothesis","volume":"291","author":"Luo","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"979606","DOI":"10.1155\/2014\/979606","article-title":"Development of dual inhibitors against Alzheimer\u2019s disease using fragment-based QSAR and molecular docking","volume":"2014","author":"Goyal","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"113492","DOI":"10.1016\/j.ejmech.2021.113492","article-title":"Dual-target compounds for Alzheimer\u2019s disease: Natural and synthetic AChE and BACE-1 dual-inhibitors and their structure-activity relationship (SAR)","volume":"221","author":"Ferreira","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2027","DOI":"10.1038\/s41591-025-03605-x","article-title":"Blood-based biomarkers of Alzheimer\u2019s disease and incident dementia in the community","volume":"31","author":"Grande","year":"2025","journal-title":"Nat. Med."},{"key":"ref_21","first-page":"CD000202","article-title":"Withdrawn: Tacrine for Alzheimer\u2019s disease","volume":"3","author":"Qizilbash","year":"2007","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"696","DOI":"10.2174\/1570159X18666191230120053","article-title":"Potential Therapeutic Approaches to Alzheimer\u2019s Disease By Bioinformatics, Cheminformatics and Predicted Adme-Tox Tools","volume":"18","author":"Avram","year":"2020","journal-title":"Curr. Neuropharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Nilewar, S.S., Chobe, S., Dudhe, P., Kumar, P.K., Lodha, S., Raut, A.D., Fern\u00e1ndez-Conde, D., Farhan, M., Muteeb, G., and Pawar, T.J. (2026). An Integrated QSAR-MD-DCCM Pipeline: A Predictive Computational Platform for the Rational Design and Dynamic Functional Validation of Dual-Target Directed Ligands. Pharmaceuticals, 19.","DOI":"10.3390\/ph19020249"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.aca.2005.09.020","article-title":"Development of immobilized membrane-based affinity columns for use in the online characterization of membrane bound proteins and for targeted affinity isolations","volume":"564","author":"Moaddel","year":"2006","journal-title":"Anal. Chim. Acta"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Bastikar, V., Bastikar, A., and Gupta, P. (2022). Quantitative structure\u2013activity relationship-based computational approaches. Computational Approaches for Novel Therapeutic and Diagnostic Designing to Mitigate SARS-CoV-2 Infection, Elsevier.","DOI":"10.1016\/B978-0-323-91172-6.00001-7"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1021\/mp100423u","article-title":"Why QSAR Fails: An Empirical Evaluation Using Conventional Computational Approach","volume":"8","author":"Huang","year":"2011","journal-title":"Mol. Pharm."},{"key":"ref_27","unstructured":"Rogers, J.P. (1996). Genetic Algorithms in Feature Selection. Principles of QSAR and Drug Design, Academic Press."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1016\/j.jmgm.2010.03.005","article-title":"Hybrid-genetic algorithm based descriptor optimization and QSAR models for predicting the biological activity of Tipranavir analogs for HIV protease inhibition","volume":"28","author":"Reddy","year":"2010","journal-title":"J. Mol. Graph. Model."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e70049","DOI":"10.1002\/cem.70049","article-title":"Predictive QSAR Models Followed by Toxicity, Molecular Docking, and Molecular Dynamics Simulation in Search of Azole Derivatives as AChE Inhibitors for the Treatment of Alzheimer\u2019s Disease","volume":"39","author":"Gupta","year":"2025","journal-title":"J. Chemom."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"104502","DOI":"10.1016\/j.arabjc.2022.104502","article-title":"SAR studies of quinoline and derivatives as potential treatments for Alzheimer\u2019s disease","volume":"16","author":"Li","year":"2022","journal-title":"Arab. J. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7223","DOI":"10.1021\/jm0503289","article-title":"Design, synthesis, and biological evaluation of dual binding site acetylcholinesterase inhibitors: New disease-modifying agents for Alzheimer\u2019s disease","volume":"48","author":"Rubio","year":"2005","journal-title":"J. Med. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1002\/ardp.201600123","article-title":"Novel tacrine-based pyrano[3\u2032,4\u2032:5,6]pyrano[2,3-b]quinolinones: Synthesis and cholinesterase inhibitory activity","volume":"349","author":"Hariri","year":"2016","journal-title":"Arch. Pharm."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.ejmech.2013.01.029","article-title":"Synthesis of tacrine-lophine hybrids via one-pot four component reaction and biological evaluation as acetyl- and butyrylcholinesterase inhibitors","volume":"62","author":"Russowsky","year":"2013","journal-title":"Eur. J. Med. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"P20","DOI":"10.1186\/1758-2946-3-S1-P20","article-title":"Online chemical modeling environment (OCHEM): Web platform for data storage, model development and publishing of chemical information","volume":"3","author":"Sushko","year":"2011","journal-title":"J. Cheminform."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2121","DOI":"10.1002\/jcc.23361","article-title":"QSARINS: A new software for the development, analysis, and validation of QSAR MLR models","volume":"34","author":"Gramatica","year":"2013","journal-title":"J. Comput. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1002\/jcc.23576","article-title":"QSARINS-chem: Insubria datasets and new QSAR\/QSPR models for environmental pollutants in QSARINS","volume":"35","author":"Gramatica","year":"2014","journal-title":"J. Comput. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"W422","DOI":"10.1093\/nar\/gkae236","article-title":"ADMETlab 3.0: An updated comprehensive online ADMET prediction platform enhanced with broader coverage, improved performance, API functionality and decision support","volume":"52","author":"Fu","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_38","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_39","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.ijbiomac.2022.05.009","article-title":"Crystal structure of human acetylcholinesterase in complex with tacrine: Implications for drug discovery","volume":"210","author":"Dileep","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"bbac087","DOI":"10.1093\/bib\/bbac087","article-title":"FitDock: Protein\u2013ligand docking by template fitting","volume":"23","author":"Yang","year":"2022","journal-title":"Brief. Bioinform."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"W159","DOI":"10.1093\/nar\/gkac394","article-title":"CB-Dock2: Improved protein\u2013ligand blind docking by integrating cavity detection, docking and homologous template fitting","volume":"50","author":"Liu","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e4792","DOI":"10.1002\/pro.4792","article-title":"UCSF ChimeraX: Tools for structure building and analysis","volume":"32","author":"Meng","year":"2023","journal-title":"Protein Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"W611","DOI":"10.1093\/nar\/gkac305","article-title":"ProteinsPlus: A comprehensive collection of web-based molecular modeling tools","volume":"50","author":"Diedrich","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"W337","DOI":"10.1093\/nar\/gkx333","article-title":"ProteinsPlus: A web portal for structure analysis of macromolecules","volume":"45","author":"Bietz","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"W48","DOI":"10.1093\/nar\/gkaa235","article-title":"ProteinsPlus: Interactive analysis of protein\u2013ligand binding interfaces","volume":"48","author":"Diedrich","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_46","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). Scalable Algorithms for Molecular Dynamics Simulations on Commodity Clusters. Proceedings of the 2006 ACM\/IEEE Conference on Supercomputing (SC\u201906), IEEE.","DOI":"10.1145\/1188455.1188544"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Nilewar, S.S., Chobe, S.S., Gurav, A.D., Kureshi, S.B., Palande, S.B., Escobar-Cabrera, J., Hern\u00e1ndez-Rosas, F., and Pawar, T.J. (2026). Galloylation-Driven Anchoring of the Asp325-Asp336 Ridge: The Molecular Logic Behind the Superior Kinetic Stabilization of HMPV Fusion Protein by Green Tea Dimeric Catechins. Molecules, 31.","DOI":"10.20944\/preprints202601.1028.v1"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.1002\/jcc.21787","article-title":"MDAnalysis: A toolkit for the analysis of molecular dynamics simulations","volume":"32","author":"Denning","year":"2011","journal-title":"J. Comput. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/pro.3330","article-title":"MolProbity: More and better reference data for improved all-atom structure validation","volume":"27","author":"Williams","year":"2018","journal-title":"Protein Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1109\/MCSE.2007.55","article-title":"Matplotlib: A 2D Graphics Environment","volume":"9","author":"Hunter","year":"2007","journal-title":"Comput. Sci. Eng."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/s41592-019-0686-2","article-title":"SciPy 1.0: Fundamental algorithms for scientific computing in Python","volume":"17","author":"Virtanen","year":"2020","journal-title":"Nat. Methods"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/s41586-020-2649-2","article-title":"Array programming with NumPy","volume":"585","author":"Harris","year":"2020","journal-title":"Nature"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1002\/prot.340110305","article-title":"Collective motions in proteins: A covariance analysis of atomic fluctuations in molecular dynamics and normal mode simulations","volume":"11","author":"Ichiye","year":"1991","journal-title":"Proteins"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/7\/3286\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T02:14:17Z","timestamp":1775441657000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/7\/3286"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,4]]},"references-count":53,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["ijms27073286"],"URL":"https:\/\/doi.org\/10.3390\/ijms27073286","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,4]]}}}