{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:44:15Z","timestamp":1792457055128,"version":"4.5.0"},"reference-count":98,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,15]],"date-time":"2021-12-15T00:00:00Z","timestamp":1639526400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006261","name":"Taif University","doi-asserted-by":"publisher","award":["TURSP-2020\/131"],"award-info":[{"award-number":["TURSP-2020\/131"]}],"id":[{"id":"10.13039\/501100006261","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Casein kinase-1 alpha (CK1\u03b1) is a multifunctional protein kinase that belongs to the serine\/threonine kinases of the CK1\u03b1 family. It is involved in various signaling pathways associated with chromosome segregation, cell metabolism, cell cycle progression, apoptosis, autophagy, etc. It has been known to involve in the progression of many diseases, including cancer, neurodegeneration, obesity, and behavioral disorders. The elevated expression of CK1\u03b1 in diseased conditions facilitates its selective targeting for therapeutic management. Here, we have performed virtual screening of phytoconstituents from the IMPPAT database seeking potential inhibitors of CK1\u03b1. First, a cluster of compounds was retrieved based on physicochemical parameters following Lipinski\u2019s rules and PAINS filter. Further, high-affinity hits against CK1\u03b1 were obtained based on their binding affinity score. Furthermore, the ADMET, PAINS, and PASS evaluation was carried out to select more potent hits. Finally, following the interaction analysis, we elucidated three phytoconstituents, Semiglabrinol, Curcusone_A, and Liriodenine, posturing considerable affinity and specificity towards the CK1\u03b1 binding pocket. The result was further evaluated by molecular dynamics (MD) simulations, dynamical cross-correlation matrix (DCCM), and principal components analysis (PCA), which revealed that binding of the selected compounds, especially Semiglabrinol, stabilizes CK1\u03b1 and leads to fewer conformational fluctuations. The MM-PBSA analysis suggested an appreciable binding affinity of all three compounds toward CK1\u03b1.<\/jats:p>","DOI":"10.3390\/pharmaceutics13122157","type":"journal-article","created":{"date-parts":[[2021,12,15]],"date-time":"2021-12-15T21:47:36Z","timestamp":1639604856000},"page":"2157","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Identification of Phytoconstituents as Potent Inhibitors of Casein Kinase-1 Alpha Using Virtual Screening and Molecular Dynamics Simulations"],"prefix":"10.3390","volume":"13","author":[{"given":"Alaa","family":"Shafie","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shama","family":"Khan","sequence":"additional","affiliation":[{"name":"Drug Discovery and Development Centre (H3D), University of Cape Town, Rondebosch 7701, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Zehra","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0399-4835","authenticated-orcid":false,"given":"Taj","family":"Mohammad","sequence":"additional","affiliation":[{"name":"Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farah","family":"Anjum","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulam Mustafa","family":"Hasan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, College of Medicine, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1102-1993","authenticated-orcid":false,"given":"Dharmendra Kumar","family":"Yadav","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Gachon University of Medicine and Science, Hambakmoeiro, Yeonsu-gu, Incheon City 21924, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3663-4940","authenticated-orcid":false,"given":"Md. Imtaiyaz","family":"Hassan","sequence":"additional","affiliation":[{"name":"Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1476-4598-13-231","article-title":"Biological functions of casein kinase 1 isoforms and putative roles in tumorigenesis","volume":"13","author":"Schittek","year":"2014","journal-title":"Mol. Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3756","DOI":"10.1002\/elps.201200345","article-title":"Quantitative proteomic analysis reveals that lipopolysaccharide induces mitogen-activated protein kinase-dependent activation in human microglial cells","volume":"33","author":"Byun","year":"2012","journal-title":"Electrophoresis"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1002\/jcp.29866","article-title":"Protein kinase C-\u03b4 interacts with and phosphorylates ARD1","volume":"236","author":"Chun","year":"2021","journal-title":"J. Cell. Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"10122","DOI":"10.1074\/jbc.M109.071381","article-title":"Src Kinase Phosphorylates RUNX3 at Tyrosine Residues and Localizes the Protein in the Cytoplasm","volume":"285","author":"Goh","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1097\/HJH.0000000000000018","article-title":"Enhanced activation of NAD(P)H","volume":"32","author":"Kim","year":"2014","journal-title":"J. Hypertens."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.jgr.2017.07.006","article-title":"Effects of fermented black ginseng on wound healing mediated by angiogenesis through the mitogen-activated protein kinase pathway in human umbilical vein endothelial cells","volume":"42","author":"Park","year":"2018","journal-title":"J. Ginseng Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s12104-011-9336-z","article-title":"Backbone resonances assignment of 19 kDa CD1 domain of human mitotic checkpoint serine\/threonine-protein kinase, Bub1","volume":"6","author":"Park","year":"2011","journal-title":"Biomol. NMR Assign."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.ceb.2014.08.003","article-title":"Casein kinase 1 and Wnt\/\u03b2-catenin signaling","volume":"31","author":"Cruciat","year":"2014","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1089\/omi.2018.0047","article-title":"New Targets for Parkinson\u2019s Disease: Adhesion G Protein-Coupled Receptor B1 is Downregulated by AMP-Activated Protein Kinase Activation","volume":"22","author":"Choi","year":"2018","journal-title":"OMICS A J. Integr. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.cbi.2018.04.023","article-title":"Oxyresveratrol ameliorates nonalcoholic fatty liver disease by regulating hepatic lipogenesis and fatty acid oxidation through liver kinase B1 and AMP-activated protein kinase","volume":"289","author":"Lee","year":"2018","journal-title":"Chem. Interact."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.cellsig.2018.09.015","article-title":"Corrigendum to \u201cAMP-activated protein kinase mediates T cell activation-induced expression of FasL and COX-2 via protein kinase C theta-dependent pathway in human Jurkat T leukemia cells\u201d","volume":"52","author":"Lee","year":"2018","journal-title":"Cell. Signal."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.fct.2016.02.022","article-title":"Octaphlorethol A, a marine algae product, exhibits antidiabetic effects in type 2 diabetic mice by activating AMP-activated protein kinase and upregulating the expression of glucose transporter 4","volume":"91","author":"Lee","year":"2016","journal-title":"Food Chem. Toxicol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1177\/0960327114561343","article-title":"Role of protein kinase C-\u03b7 in cigarette smoke extract-induced apoptosis in MRC-5-cells","volume":"34","author":"Son","year":"2015","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.1016\/j.athoracsur.2016.03.118","article-title":"Which Variables Should be Considered as Confounders of p38-Mitogen Activated Protein Kinase Activation Measurements?","volume":"102","author":"Son","year":"2016","journal-title":"Ann. Thorac. Surg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4937","DOI":"10.1158\/0008-5472.CAN-15-1113","article-title":"Inhibition of casein kinase 1 alpha prevents acquired drug resistance to Erlotinib in EGFR-mutant non\u2013small cell lung cancer","volume":"75","author":"Lantermann","year":"2015","journal-title":"Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Janovsk\u00e1, P., Normant, E., Miskin, H., and Bryja, V. (2020). Targeting Casein Kinase 1 (CK1) in Hematological Cancers. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21239026"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1159\/000087137","article-title":"The role of the casein kinase 1 (CK1) family in different signaling pathways linked to cancer development","volume":"28","author":"Knippschild","year":"2005","journal-title":"Oncol. Res. Treat."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12964-018-0236-z","article-title":"Casein kinase 1\u03b1: Biological mechanisms and theranostic potential","volume":"16","author":"Jiang","year":"2018","journal-title":"Cell Commun. Signal."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"172596","DOI":"10.1016\/j.ejphar.2019.172596","article-title":"Clomiphene promotes browning of white adipocytes via casein kinase-2 inhibition","volume":"861","author":"Kim","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Tran, N., and Chun, K.-H. (2021). ROCK2-Specific Inhibitor KD025 Suppresses Adipocyte Differentiation by Inhibiting Casein Kinase 2. Molecules, 26.","DOI":"10.3390\/molecules26164747"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1002\/j.1460-2075.1995.tb07082.x","article-title":"Crystal structure of casein kinase-1, a phosphate-directed protein kinase","volume":"14","author":"Xu","year":"1995","journal-title":"EMBO J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.cell.2018.07.045","article-title":"Small molecules co-targeting CKI\u03b1 and the transcriptional kinases CDK7\/9 control AML in preclinical models","volume":"175","author":"Minzel","year":"2018","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-020-77978-z","article-title":"Discovery of a novel fibroblast activation protein (FAP) inhibitor, BR103354, with anti-diabetic and anti-steatotic effects","volume":"10","author":"Cho","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Lee, S.-M., Kim, M.-S., Hayat, F., and Shin, D. (2019). Recent advances in the discovery of novel antiprotozoal agents. Molecules, 24.","DOI":"10.3390\/molecules24213886"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12859-017-1558-3","article-title":"Drug voyager: A computational platform for exploring unintended drug action","volume":"18","author":"Oh","year":"2017","journal-title":"BMC Bioinform."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"14720","DOI":"10.1021\/acsomega.0c01511","article-title":"Identification of sphingosine kinase-1 inhibitors from bioactive natural products targeting cancer therapy","volume":"5","author":"Jairajpuri","year":"2020","journal-title":"ACS Omega"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1080\/07391102.2018.1468282","article-title":"Identification and evaluation of bioactive natural products as potential inhibitors of human microtubule affinity-regulating kinase 4 (MARK4)","volume":"37","author":"Mohammad","year":"2019","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Alam, M., Ali, S., Mohammad, T., Hasan, G.M., Yadav, D.K., and Hassan, M. (2021). B Cell Lymphoma 2: A Potential Therapeutic Target for Cancer Therapy. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910442"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1021\/acs.jcim.5b00484","article-title":"Ensemble-Based Virtual Screening Led to the Discovery of New Classes of Potent Tyrosinase Inhibitors","volume":"56","author":"Choi","year":"2016","journal-title":"J. Chem. Inf. Model."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"14921","DOI":"10.1038\/s41598-018-33354-6","article-title":"Identification of novel acetylcholinesterase inhibitors designed by pharmacophore-based virtual screening, molecular docking and bioassay","volume":"8","author":"Jang","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Lee, J.H., Cho, S.J., and Kim, M.-H. (2018). Discovery of CNS-Like D3R-Selective Antagonists Using 3D Pharmacophore Guided Virtual screening. Molecules, 23.","DOI":"10.20944\/preprints201807.0427.v1"},{"key":"ref_32","first-page":"862","article-title":"Virtual screening of chemical libraries","volume":"432","author":"Shoichet","year":"2004","journal-title":"Nat. Cell Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.2174\/1568026618666181025114157","article-title":"Advancements in docking and molecular dynamics simulations towards ligand-receptor interactions and structure-function relationships","volume":"18","author":"Naqvi","year":"2018","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1002\/jcb.29933","article-title":"In silico identification of prolyl hydroxylase inhibitor by per-residue energy decomposition-based pharmacophore approach","volume":"122","author":"Teli","year":"2021","journal-title":"J. Cell. Biochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"250","DOI":"10.3389\/fchem.2020.00250","article-title":"Computational modeling on aquaporin-3 as skin cancer target: A virtual screening study","volume":"8","author":"Yadav","year":"2020","journal-title":"Front. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Waseem, R., Anwar, S., Khan, S., Shamsi, A., Hassan, M., Anjum, F., Shafie, A., Islam, A., and Yadav, D.K. (2021). MAP\/Microtubule Affinity Regulating Kinase 4 Inhibitory Potential of Irisin: A New Therapeutic Strategy to Combat Cancer and Alzheimer\u2019s Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222010986"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1080\/07391102.2020.1714480","article-title":"In silico identification of hydantoin derivatives: A novel natural prolyl hydroxylase inhibitor","volume":"39","author":"Teli","year":"2021","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.ddtec.2004.11.007","article-title":"Lead-and drug-like compounds: The rule-of-five revolution","volume":"1","author":"Lipinski","year":"2004","journal-title":"Drug Discov. Today Technol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1021\/acs.jnatprod.5b00947","article-title":"Feeling nature\u2019s PAINS: Natural products, natural product drugs, and pan assay interference compounds (PAINS)","volume":"79","author":"Baell","year":"2016","journal-title":"J. Nat. Prod."},{"key":"ref_40","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_41","doi-asserted-by":"crossref","unstructured":"Koparde, A.A., Doijad, R.C., and Magdum, C.S. (2019). Natural products in drug discovery. Pharmacognosy-Medicinal Plants, IntechOpen.","DOI":"10.5772\/intechopen.82860"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0163-7258(03)00042-1","article-title":"Natural products for cancer prevention: A global perspective","volume":"99","author":"Reddy","year":"2003","journal-title":"Pharmacol. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"8.14.11","DOI":"10.1002\/0471250953.bi0814s24","article-title":"Using autodock for ligand-receptor docking","volume":"24","author":"Morris","year":"2008","journal-title":"Curr. Protoc. Bioinform."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"bbaa279","DOI":"10.1093\/bib\/bbaa279","article-title":"InstaDock: A single-click graphical user interface for molecular docking-based virtual high-throughput screening","volume":"22","author":"Mohammad","year":"2021","journal-title":"Brief Bioinform."},{"key":"ref_45","first-page":"82","article-title":"Pymol: An open-source molecular graphics tool","volume":"40","author":"DeLano","year":"2002","journal-title":"CCP4 Newsl. Protein Crystallogr."},{"key":"ref_46","unstructured":"Dassault Systemes BIOVIA (2008). Discovery Studio, Accelrys [2.1], Dassault Systemes BIOVIA."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-018-22631-z","article-title":"IMPPAT: A curated database of I ndian M edicinal P lants, P hytochemistry A nd T herapeutics","volume":"8","author":"Mohanraj","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep42717","article-title":"SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules","volume":"7","author":"Daina","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4066","DOI":"10.1021\/acs.jmedchem.5b00104","article-title":"pkCSM: Predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures","volume":"58","author":"Pires","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1016\/j.bmcl.2018.03.057","article-title":"Synthesis, biological evaluation and molecular docking study of 1-amino-2-aroylnaphthalenes against prostate cancer","volume":"28","author":"Rai","year":"2018","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.ejmech.2017.07.076","article-title":"Novel Gomisin B analogues as potential cytotoxic agents: Design, synthesis, biological evaluation and docking studies","volume":"139","author":"Poornima","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4625","DOI":"10.1080\/07391102.2019.1682052","article-title":"Virtual high-throughput screening of natural compounds in-search of potential inhibitors for protection of telomeres 1 (POT1)","volume":"38","author":"Amir","year":"2020","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Mohammad, T., Siddiqui, S., Shamsi, A., Alajmi, M.F., Hussain, A., Islam, A., Ahmad, F., and Hassan, M. (2020). Virtual screening approach to identify high-affinity inhibitors of serum and glucocorticoid-regulated kinase 1 among bioactive natural products: Combined molecular docking and simulation studies. Molecules, 25.","DOI":"10.3390\/molecules25040823"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1002\/cmdc.201800318","article-title":"Discovery of Aporphine Analogues as Potential Antiplatelet and Antioxidant Agents: Design, Synthesis, Structure-Activity Relationships, Biological Evaluations, and in silico Molecular Docking Studies","volume":"13","author":"Sharma","year":"2018","journal-title":"ChemMedChem"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Gimeno, A., Montes, M.J.O., Tom\u00e1s-Hern\u00e1ndez, S., Cereto-Massagu\u00e9, A., Beltr\u00e1n-Deb\u00f3n, R., Mulero, M., Pujadas, G., and Garcia-Vallv\u00e9, S. (2019). The Light and Dark Sides of Virtual Screening: What Is There to Know?. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20061375"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1002\/cmdc.202000045","article-title":"Design, Synthesis, Structure-Activity Relationship and Docking Studies of Novel Functionalized Arylvinyl-1, 2, 4-Trioxanes as Potent Antiplasmodial as well as Anticancer Agents","volume":"15","author":"Tiwari","year":"2020","journal-title":"ChemMedChem"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"36","DOI":"10.3389\/fchem.2017.00036","article-title":"Docking based 3D-QSAR study of tricyclic guanidine analogues of batzelladine K as anti-malarial agents","volume":"5","author":"Ahmed","year":"2017","journal-title":"Front. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2174\/1568026621666210426124719","article-title":"In-silico Studies and Wet-Lab Validation of Camptothecin Derivatives for Anti-Cancer Activity Against Liver (HepG2) and Lung (A549) Cancer Cell Lines","volume":"21","author":"Kalani","year":"2021","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_59","first-page":"1","article-title":"Structural ensemble-based docking simulation and biophysical studies discovered new inhibitors of Hsp90 N-terminal domain","volume":"8","author":"Kim","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_60","first-page":"4","article-title":"Pharmacokinetic and molecular docking studies to design antimalarial compounds targeting Actin I","volume":"15","author":"Guleria","year":"2021","journal-title":"Int. J. Health Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3570","DOI":"10.1002\/jcb.29640","article-title":"Ligand-based pharmacophore modeling and docking studies on vitamin D receptor inhibitors","volume":"121","author":"Yadav","year":"2020","journal-title":"J. Cell. Biochem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"101","DOI":"10.3389\/fchem.2018.00101","article-title":"Insights into the bifunctional aphidicolan-16-\u00df-ol synthase through rapid biomolecular modeling approaches","volume":"6","author":"Hirte","year":"2018","journal-title":"Front. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1016\/j.phymed.2012.04.009","article-title":"Effect of diallyl disulfide on insulin-like growth factor signaling molecules involved in cell survival and proliferation of human prostate cancer cells in vitro and in silico approach through docking analysis","volume":"19","author":"Arunkumar","year":"2012","journal-title":"Phytomedicine"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0010-4655(95)00041-D","article-title":"AMBER, a package of computer programs for applying molecular mechanics, normal mode analysis, molecular dynamics and free energy calculations to simulate the structural and energetic properties of molecules","volume":"91","author":"Pearlman","year":"1995","journal-title":"Comput. Phys. Commun."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4611","DOI":"10.1021\/acsomega.9b04233","article-title":"Fast, accurate, and reliable protocols for routine calculations of protein\u2013ligand binding affinities in drug design projects using AMBER GPU-TI with ff14SB\/GAFF","volume":"5","author":"He","year":"2020","journal-title":"ACS Omega"},{"key":"ref_66","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_67","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1002\/(SICI)1096-987X(20000130)21:2<132::AID-JCC5>3.0.CO;2-P","article-title":"Fast, efficient generation of high-quality atomic charges. AM1-BCC model: I. Method","volume":"21","author":"Jakalian","year":"2000","journal-title":"J. Comput. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"9954","DOI":"10.1021\/jp003020w","article-title":"Structure and dynamics of the TIP3P, SPC, and SPC\/E water models at 298 K","volume":"105","author":"Mark","year":"2001","journal-title":"J. Phys. Chem. A"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3084","DOI":"10.1021\/ct400341p","article-title":"PTRAJ and CPPTRAJ: Software for processing and analysis of molecular dynamics trajectory data","volume":"9","author":"Roe","year":"2013","journal-title":"J. Chem. Theory Comput."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1002\/prot.24574","article-title":"Detecting protein atom correlations using correlation of probability of recurrence","volume":"82","author":"Fataftah","year":"2014","journal-title":"Proteins: Struct. Funct. Bioinform."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"David, C.C., and Jacobs, D.J. (2014). Principal component analysis: A method for determining the essential dynamics of proteins. Protein Dynamics, Humana Press.","DOI":"10.1007\/978-1-62703-658-0_11"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"41","DOI":"10.3389\/fmolb.2019.00041","article-title":"Structural analysis and conformational dynamics of STN1 gene mutations involved in coat plus syndrome","volume":"6","author":"Amir","year":"2019","journal-title":"Front. Mol. Biosci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.1016\/j.sjbs.2021.01.040","article-title":"Identification of natural compounds as potent inhibitors of SARS-CoV-2 main protease using combined docking and molecular dynamics simulations","volume":"28","author":"Jairajpuri","year":"2021","journal-title":"Saudi J. Biol. Sci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/j.jmgm.2009.01.006","article-title":"Free-energy landscape, principal component analysis, and structural clustering to identify representative conformations from molecular dynamics simulations: The myoglobin case","volume":"27","author":"Papaleo","year":"2009","journal-title":"J. Mol. Graph. Model."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1517\/17460441.2015.1032936","article-title":"The MM\/PBSA and MM\/GBSA methods to estimate ligand-binding affinities","volume":"10","author":"Genheden","year":"2015","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_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","unstructured":"Razia, S., Park, H., Shin, E., Shim, K.-S., Cho, E., and Kim, S.-Y. (2021). Effects of Aloe vera Flower Extract and Its Active Constituent Isoorientin on Skin Moisturization via Regulating Involucrin Expression: In Vitro and Molecular Docking Studies. Molecules, 26.","DOI":"10.3390\/molecules26092626"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.2147\/DDDT.S130601","article-title":"Molecular docking, QSAR and ADMET studies of withanolide analogs against breast cancer","volume":"ume 11","author":"Yadav","year":"2017","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1089\/omi.2021.0107","article-title":"Phytoconstituents and Medicinal Plants for Anticancer Drug Discovery: Computational Identification of Potent Inhibitors of PIM1 Kinase","volume":"25","author":"Anjum","year":"2021","journal-title":"OMICS A J. Integr. Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2491","DOI":"10.1080\/07391102.2014.1002006","article-title":"In silicocharacterization of binding mode of CCR8 inhibitor: Homology modeling, docking and membrane based MD simulation study","volume":"33","author":"Gadhe","year":"2015","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"191","DOI":"10.4062\/biomolther.2015.122","article-title":"Quercetin Directly Interacts with Vitamin D Receptor (VDR): Structural Implication of VDR Activation by Quercetin","volume":"24","author":"Lee","year":"2016","journal-title":"Biomol. Ther."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.2174\/1568026619666190816101948","article-title":"Virtual Screening Techniques in Drug Discovery: Review and Recent Applications","volume":"19","author":"Rocha","year":"2019","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Maia, E.H.B., Assis, L.C., de Oliveira, T.A., Da Silva, A.M., and Taranto, A.G. (2020). Structure-Based Virtual Screening: From Classical to Artificial Intelligence. Front. Chem., 8.","DOI":"10.3389\/fchem.2020.00343"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"644","DOI":"10.3389\/fphar.2018.00644","article-title":"Insight Into the Molecular Dynamic Simulation Studies of Reactive Oxygen Species in Native Skin Membrane","volume":"9","author":"Yadav","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_85","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_86","doi-asserted-by":"crossref","unstructured":"Hubbard, R.E., and Haider, M.K. (2010). Hydrogen bonds in proteins: Role and strength. eLS.","DOI":"10.1002\/9780470015902.a0003011.pub2"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1021\/js9802493","article-title":"Secondary structure and protein deamidation","volume":"88","author":"Xie","year":"1999","journal-title":"J. Pharm. Sci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"3374","DOI":"10.1016\/j.bmcl.2017.06.011","article-title":"Synthesis and biological evaluation of caffeic acid derivatives as potent inhibitors of \u03b1-MSH-stimulated melanogenesis","volume":"27","author":"Jo","year":"2017","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.bbapap.2015.02.009","article-title":"Structural insight into the interaction between the Hox and HMGB1 and understanding of the HMGB1-enhancing effect of Hox-DNA binding","volume":"1854","author":"Kim","year":"2015","journal-title":"Biochim. Biophys. Acta (BBA)-Proteins Proteom."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"7109","DOI":"10.3390\/ijms13067109","article-title":"Structural Analysis of Hypothetical Proteins from Helicobacter pylori: An Approach to Estimate Functions of Unknown or Hypothetical Proteins","volume":"13","author":"Park","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1017\/S0033583519000027","article-title":"Dynamics of proteins in solution","volume":"52","author":"Grimaldo","year":"2019","journal-title":"Q. Rev. Biophys."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Mishra, S.K., and Jernigan, R.L. (2018). Protein dynamic communities from elastic network models align closely to the communities defined by molecular dynamics. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0199225"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1038\/nmeth.4346","article-title":"Points of significance: Principal component analysis","volume":"14","author":"Lever","year":"2017","journal-title":"Nat. Methods"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"3610","DOI":"10.1080\/07391102.2019.1664937","article-title":"Identification and evaluation of glutathione conjugate gamma-l-glutamyl-l-cysteine for improved drug delivery to the brain","volume":"38","author":"Fatima","year":"2020","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Ali, S., Khan, F.I., Mohammad, T., Lan, D., Hassan, M., and Wang, Y. (2019). Identification and evaluation of inhibitors of lipase from Malassezia restricta using virtual high-throughput screening and molecular dynamics studies. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20040884"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1016\/j.ijbiomac.2019.06.158","article-title":"Investigation of inhibitory potential of quercetin to the pyruvate dehydrogenase kinase 3: Towards implications in anticancer therapy","volume":"136","author":"Dahiya","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Khan, A., Mohammad, T., Shamsi, A., Hussain, A., Alajmi, M.F., Husain, S.A., Iqbal, M.A., and Hassan, M.I. (2021). Identification of plant-based hexokinase 2 inhibitors: Combined molecular docking and dynamics simulation studies. J. Biomol. Struct. Dyn., 1\u201313.","DOI":"10.1080\/07391102.2021.1942217"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"e1455","DOI":"10.1002\/wcms.1455","article-title":"Ligand binding free energy and kinetics calculation in 2020","volume":"10","author":"Limongelli","year":"2020","journal-title":"Wiley Interdiscip. Rev. Comput. Mol. Sci."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/13\/12\/2157\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:48:20Z","timestamp":1760168900000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/13\/12\/2157"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,15]]},"references-count":98,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["pharmaceutics13122157"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics13122157","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,15]]}}}