{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:36:36Z","timestamp":1760146596311,"version":"build-2065373602"},"reference-count":112,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T00:00:00Z","timestamp":1731888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Blavatnik Family Foundation award","award":["1626378","2117625"],"award-info":[{"award-number":["1626378","2117625"]}]},{"name":"Fordham University Research Grants","award":["1626378","2117625"],"award-info":[{"award-number":["1626378","2117625"]}]},{"name":"Henry Luce Foundation for Clare Boothe Luce Scholarship","award":["1626378","2117625"],"award-info":[{"award-number":["1626378","2117625"]}]},{"name":"Barry Goldwater Scholarship","award":["1626378","2117625"],"award-info":[{"award-number":["1626378","2117625"]}]},{"name":"NSF-MRI","award":["1626378","2117625"],"award-info":[{"award-number":["1626378","2117625"]}]},{"name":"Barry Goldwater Scholarship","award":["1626378","2117625"],"award-info":[{"award-number":["1626378","2117625"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomimetics"],"abstract":"<jats:p>Alpha-synuclein (ASyn) is a protein that is known to play a critical role in Parkinson\u2019s disease (PD) due to its propensity for misfolding and aggregation. Furthermore, this process leads to oxidative stress and the formation of free radicals that cause neuronal damage. In this study, we have utilized a biomimetic approach to design new peptides derived from marine natural resources. The peptides were designed using a peptide scrambling approach where antioxidant moieties were combined with fibrillary inhibition motifs in order to design peptides that would have a dual targeting effect on ASyn misfolding. Of the 20 designed peptides, 12 were selected for examining binding interactions through molecular docking and molecular dynamics approaches, which revealed that the peptides were binding to the pre-NAC and NAC (non-amyloid component) domain residues such as Tyr39, Asn65, Gly86, and Ala85, among others. Because ASyn filaments derived from Lewy body dementia (LBD) have a different secondary structure compared to pathogenic ASyn fibrils, both forms were tested computationally. Five of those peptides were utilized for laboratory validation based on those results. The binding interactions with fibrils were confirmed using surface plasmon resonance studies, where EQALMPWIWYWKDPNGS, PYYYWKDPNGS, and PYYYWKELAQM showed higher binding. Secondary structural analyses revealed their ability to induce conformational changes in ASyn fibrils. Additionally, PYYYWKDPNGS and PYYYWKELAQM also demonstrated antioxidant properties. This study provides insight into the binding interactions of varying forms of ASyn implicated in PD. The peptides may be further investigated for mitigating fibrillation at the cellular level and may have the potential to target ASyn.<\/jats:p>","DOI":"10.3390\/biomimetics9110705","type":"journal-article","created":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T10:44:37Z","timestamp":1732013077000},"page":"705","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the Potential of Biomimetic Peptides in Targeting Fibrillar and Filamentous Alpha-Synuclein\u2014An In Silico and Experimental Approach to Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"9","author":[{"given":"Sophia A.","family":"Frantzeskos","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry, Fordham University, 441 East Fordham Road, Bronx, NY 10458, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1224-8578","authenticated-orcid":false,"given":"Mary A.","family":"Biggs","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Fordham University, 441 East Fordham Road, Bronx, NY 10458, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6987-9717","authenticated-orcid":false,"given":"Ipsita A.","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Fordham University, 441 East Fordham Road, Bronx, NY 10458, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/978-94-007-5416-4_16","article-title":"Parkinson\u2019s Disease","volume":"65","author":"Mhyre","year":"2012","journal-title":"Subcell Biochem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"259","DOI":"10.31887\/DCNS.2004.6.3\/galexander","article-title":"Biology of Parkinson\u2019s Disease: Pathogenesis and pathophysiology of a multisystem neurodegenerative disorder","volume":"6","author":"Alexander","year":"2004","journal-title":"Dialogues Clin. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Guatteo, E., Berretta, N., Monda, V., Ledonne, A., and Mercuri, N.B. (2022). Pathophysiological features of nigral dopaminergic neurons in animal models of Parkinson\u2019s disease. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23094508"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s00401-010-0711-0","article-title":"The synaptic pathology of alpha-synuclein aggregation in dementia with Lewy bodies, Parkinson\u2019s disease and Parkinson\u2019s disease dementia","volume":"120","year":"2010","journal-title":"Acta Neuropathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.parkreldis.2014.01.011","article-title":"CSF \u03b1-synuclein and UCH-L1 levels in Parkinson\u2019s disease and atypical parkinsonian disorders","volume":"20","author":"Mondello","year":"2014","journal-title":"Park. Relat. Disord."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.pneurobio.2004.05.002","article-title":"Genes, proteins, and neurotoxins involved in Parkinson\u2019s disease","volume":"73","author":"Schober","year":"2004","journal-title":"Prog. Neurobiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/S0140-6736(14)61393-3","article-title":"Parkinson\u2019s disease","volume":"386","author":"Kalia","year":"2015","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"a009399","DOI":"10.1101\/cshperspect.a009399","article-title":"\u03b1-Synuclein in Parkinson\u2019s Disease","volume":"2","author":"Stefanis","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_9","first-page":"699","article-title":"The synaptic function of \u03b1-Synuclein","volume":"5","year":"2015","journal-title":"J. Park. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S26","DOI":"10.1002\/ana.10483","article-title":"Oxidative stress in Parkinson\u2019s disease","volume":"53","author":"Jenner","year":"2003","journal-title":"Ann. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1002\/mds.23376","article-title":"Common variants in PARK loci and related genese and Parkinson\u2019s disease","volume":"26","author":"Chung","year":"2011","journal-title":"Mov. Disord."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Siddiqui, I.J., Pervaiz, N., and Abbasi, A.A. (2016). The Parkinson Disease gene SNCA: Evolutionary and structural insights with pathological implication. Sci. Rep., 6.","DOI":"10.1038\/srep24475"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.brainres.2012.04.014","article-title":"From \u03b1-synuclein to synaptic dysfunctions: New insights into the pathophysiology of Parkinson\u2019s disease","volume":"1476","author":"Navarria","year":"2012","journal-title":"Brain Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"7871","DOI":"10.1021\/bi030086j","article-title":"Zeroing in on the pathogenic form of alpha-synuclein and its mechanism of neurotoxicity in Parkinson\u2019s disease","volume":"42","author":"Volles","year":"2003","journal-title":"Biochemistry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1016\/j.stemcr.2016.08.012","article-title":"Parkin and PINK1 patient iPSC-derived midbrain dopamine neurons exhibit mitochondrial dysfunction and alpha-Synuclein accumulation","volume":"7","author":"Chung","year":"2016","journal-title":"Stem Cell Rep."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Vidov\u00edc, M., and Rikalovic, M.G. (2022). Alpha-Synuclein Aggregation Pathway in Parkinson\u2019s Disease: Current Status and Novel Therapeutic Approaches. Cells, 11.","DOI":"10.3390\/cells11111732"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1089\/ars.2015.6343","article-title":"Alpha-Synuclein oligomers interact with metal ions to induce oxidative stress and neuronal death in Parkinson\u2019s disease","volume":"24","author":"Deas","year":"2016","journal-title":"Antioxid. Redox Signal."},{"key":"ref_18","first-page":"205","article-title":"Generation of ferric iron links oxidative stress to alpha-synuclein oligomer formation","volume":"1","author":"Levin","year":"2011","journal-title":"J. Park. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"507","DOI":"10.2174\/1568026013394822","article-title":"Production of reactive oxygen species from aggregating proteins implicated in Alzheimer\u2019s disease, Parkinson\u2019s disease and other neurodegenerative diseases","volume":"1","author":"Tabner","year":"2001","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.neuroscience.2013.07.058","article-title":"Iron deficiency alters expression of dopamine-related genes in the ventral midbrain in mice","volume":"252","author":"Jellen","year":"2013","journal-title":"Neuroscience"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"28849","DOI":"10.1074\/jbc.274.41.28849","article-title":"Role of cytochrome c as a stimulator of \u03b1-synuclein aggregation in Lewy body disease","volume":"274","author":"Hashimoto","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"13604","DOI":"10.1021\/bi801884z","article-title":"Alpha-Synuclein conformation affects its tyrosine-dependent oxidative aggregation","volume":"47","author":"Ruf","year":"2008","journal-title":"Biochemistry"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1007\/s10787-017-0402-8","article-title":"Curcumin affords neuroprotection and inhibits \u03b1-synuclein aggregation in lipopolysaccharide-induced Parkinson\u2019s disease model","volume":"26","author":"Sharma","year":"2018","journal-title":"Inflammopharmacology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1007\/s10787-021-00886-9","article-title":"Curcumin protects dopaminergic neurons against inflammation-mediated damage and improves motor dysfunction induced by single intranigral lipopolysaccharide injecton","volume":"29","author":"Sharma","year":"2017","journal-title":"Inflammopharmacology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S0022-510X(03)00184-9","article-title":"Plasma levels of antioxidant vitamins C and E are decreased in vascular parkinsonism","volume":"215","author":"Paraskevas","year":"2003","journal-title":"J. Neurol. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Zhao, N., Yang, X., Calvelli, H.R., Cao, Y., Francis, N.L., Chmielowski, R.A., Jospeh, L.B., Pang, Z.P., Uhrich, K.E., and Baum, J. (2020). Antioxidant Nanoparticles for Concerted Inhibition of \u03b1-Synuclein Fibrillization, and Attenuation of Microglial Intracellular Aggregation and Activation. Front. Bioeng. Biotechnol., 8.","DOI":"10.3389\/fbioe.2020.00112"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1007\/s00702-023-02692-9","article-title":"L-DOPA-therapy in Parkinson\u2019s disease: Some personal reflections on L-DOPA therapy from Vienna and Berlin","volume":"130","author":"Riederer","year":"2023","journal-title":"J. Neural Transm."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1080\/17425255.2020.1750596","article-title":"Pharmacokinetics and pharmacodynamics of levodopa\/carbidopa co-therapies for Parkinson\u2019s disease","volume":"16","year":"2020","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_29","first-page":"1465","article-title":"Amantadine in Parkinson\u2019s disease","volume":"1","author":"Crosby","year":"2003","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"100623","DOI":"10.1016\/j.bbih.2023.100623","article-title":"Effects of hydrogen gas inhalation on L-DOPA-induced dyskinesia","volume":"30","author":"Nascimento","year":"2023","journal-title":"Brain Behav. Immun. Health"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1097\/WNF.0b013e318255838b","article-title":"Selegiline: A reappraisal of its role in Parkinson disease","volume":"35","author":"Fabbrini","year":"2012","journal-title":"Clin. Neuropharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.cca.2021.08.009","article-title":"Dopamine in Parkinson\u2019s disease","volume":"522","author":"Latif","year":"2021","journal-title":"Clin. Chim. Acta"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Rossino, G., Marchese, E., Galli, G., Verde, F., Finizio, M., Serra, M., Linciano, P., and Collina, S. (2023). Peptides as Therapeutic Agents: Challenges and Opportunities in the Green Transition Era. Molecules, 28.","DOI":"10.3390\/molecules28207165"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1111\/cbdd.12055","article-title":"The Future of Peptide-based Drugs","volume":"81","author":"Craik","year":"2013","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/s41392-022-00904-4","article-title":"Therapeutic peptides: Current applications and future directions","volume":"7","author":"Wang","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.4155\/fmc.10.259","article-title":"Design and development of peptides and peptide mimetics as antagonists for therapeutic intervention","volume":"2","author":"Mason","year":"2010","journal-title":"Fut. Med. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1007\/s12264-019-00407-3","article-title":"Neuroprotective Effects of Brain-Gut Peptides: A Potential Therapy for Parkinson\u2019s Disease","volume":"35","author":"Dong","year":"2019","journal-title":"Neurosci. Bull."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1016\/j.drudis.2016.01.013","article-title":"The glucagon-like peptide 1 (GLP) receptor as a therapeutic target in Parkinson\u2019s disease: Mechanisms of action","volume":"21","author":"Athauda","year":"2016","journal-title":"Drug Discov. Today"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.neulet.2008.08.047","article-title":"Mutated recombinant human glucagon-like peptide-1 protects SH-SY5Y cells from apoptosis induced by amyloid-\u03b2 peptide (1\u201342)","volume":"444","author":"Qin","year":"2008","journal-title":"Neurosci. Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1007\/s12031-015-0647-x","article-title":"CSF \u03b2-Amyloid 1\u201342 Predicts Progression to Cognitive Impairment in Newly Diagnosed Parkinson Disease","volume":"58","author":"Terrelonge","year":"2016","journal-title":"J. Mol. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3217","DOI":"10.1093\/brain\/aww238","article-title":"A de nevo compound targeting \u03b1-synuclein improves deficits in models of Parkinson\u2019s disease","volume":"139","author":"Wrasidlo","year":"2016","journal-title":"Brain"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e2217835120","DOI":"10.1073\/pnas.2217835120","article-title":"Small molecules disaggregate alpha-synuclein and prevent seeding from patient brain-derived fibrils","volume":"120","author":"Murray","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1007\/s00401-013-1114-9","article-title":"Anle138b: A novel oligomer modulator for disease-modifying therapy of neurodegenerative diseases such as prion and Parkinson\u2019s disease","volume":"125","author":"Wagner","year":"2013","journal-title":"Acta Neuropathol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"5385","DOI":"10.1038\/s41467-022-32797-w","article-title":"The clinical drug candidate anle138b binds in a cavity of lipidic \u03b1-synuclein fibrils","volume":"13","author":"Antonschmidt","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Gnaraj, C., Sekar, M., Fuloria, S., Swain, S.S., Gan, S.H., Chidambaram, K., Rani, N.N.I.M., Balan, T., Stephenie, S., and Lum, P.T. (2022). In Silico Molecular Docking Analysis of Karanjin against Alzheimer\u2019s and Parkinson\u2019s Diseases as a Potential Natural Lead Molecule for New Drug Design, Development and Therapy. Molecules, 27.","DOI":"10.3390\/molecules27092834"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Jahan, I., Ahmad, A., and Deep, S. (2023). Effect of flavonoids on the destabilization of \u03b1-synuclein fibrils and their conversion to amorphous aggregate: A molecular dynamics simulation and experimental study. Biochim. Biophys. Acta (BBA)-Proteins Proteom., 1871.","DOI":"10.1016\/j.bbapap.2023.140951"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Mooney, C., Haslam, N., Pollastri, G., and Shields, D. (2012). Towards the improved discovery and design of functional peptides: Common features of diverse classes permit generalized prediction of bioactivity. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0045012"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Oh, Y., Ahn, C.B., Cho, W.H., Yoon, N.Y., and Je, J.Y. (2020). Anti-Osteoporotic Effects of Antioxidant Peptides PIISVYWK and FSVVPSPK from Mytilus edulis on Ovariectomized Mice. Antioxidants, 9.","DOI":"10.3390\/antiox9090866"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.algal.2018.09.028","article-title":"Radical scavenging property of a novel peptide derived from C-terminal SOD domain of superoxide dismutase enzyme in Arhtrospira platensis","volume":"35","author":"Sannasimuthu","year":"2018","journal-title":"Algal Res."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Marasinghe, C.K., Jung, W.K., and Je, J.Y. (2022). Anti-inflammatory action of ark shell (Scapharca subcrenata) protein hydrolysate in LPS-stimulated RAW264.7 murine macrophages. J. Food Biochem., 46.","DOI":"10.1111\/jfbc.14493"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.ijbiomac.2019.11.222","article-title":"Both beta sheet breaker and alpha helix forming pentapeptide inhibits protein fibrillation: Implication for the treatment of amyloid disorders","volume":"143","author":"Siddiqi","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Wojewska, M., Otero-Jiminez, M., Gujjarro-Nuez, J., and Alegre-Abarrategui, J. (2023). Beyond strains: Molecular diversity in Alpha-Synuclein at the center of disease heterogeneity. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241713199"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Landureau, M., Redeker, V., Bellande, T., Eyquem, S., and Melki, R. (2021). The differential solvent exposure of N-terminal residues provides \u201cfingerprints\u201d of alpha-synuclein fibrillar polymorphs. J. Biol. Chem., 296.","DOI":"10.1016\/j.jbc.2021.100737"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Olsen, T.H., Yesiltas, B., Marin, F.I., Pertseva, M., Garcia-Moreno, P., Gregersen, S., Overgaard, M., Jacobsen, C., Lund, O., and Hansen, E. (2020). AnOxPePred: Using deep learning for the prediction of antioxidative properties of peptides. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-78319-w"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Conchillo-Sol\u00e9, O., de Groot, N.S., Avil\u00e9s, F.X., Vendrell, J., Daura, X., and Ventura, S. (2007). AGGRESCAN: A server for the prediction and evaluation of \u201chot spots\u201d of aggregation in polypeptides. BMC Bioinform., 8.","DOI":"10.1186\/1471-2105-8-65"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"100014","DOI":"10.1016\/j.crmeth.2021.100014","article-title":"Folding non-homologous proteins by coupling deep-learning contact maps with I-Tasser assembly simulations","volume":"1","author":"Zheng","year":"2021","journal-title":"Cell Rep. Methods"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1038\/s41586-022-05319-3","article-title":"Structures of \u03b1-synuclein filaments from human brains with Lewy pathology","volume":"610","author":"Yang","year":"2022","journal-title":"Nature"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1038\/nsmb.3194","article-title":"Solid-state NMR structure of a pathogenic fibril of full-length human \u03b1-synuclein","volume":"23","author":"Tuttle","year":"2016","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_59","unstructured":"(The PyMOL Molecular Graphics System, 2021). The PyMOL Molecular Graphics System, Version 2.5."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1021\/ci800324m","article-title":"Identifying and characterizing binding sites and assessing druggability","volume":"49","author":"Halgren","year":"2009","journal-title":"J. Chem. Inf. Model."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1111\/j.1747-0285.2007.00483.x","article-title":"New method for fast and accurate binding-site identification and analysis","volume":"69","author":"Halgren","year":"2007","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3891","DOI":"10.1021\/acs.jcim.1c00203","article-title":"AutoDock Vina 1.2.0: New Docking Methods, Expanded Force Field, and Python Bindings","volume":"61","author":"Eberhardt","year":"2021","journal-title":"J. Chem. Inf. Model."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.pbiomolbio.2014.05.006","article-title":"Polypharmacology rescored: Protein-ligand interaction profiles for remote binding site similarity assessment","volume":"116","author":"Salentin","year":"2014","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"W443","DOI":"10.1093\/nar\/gkv315","article-title":"PLIP: Fully automated protein-ligand interaction profiler","volume":"43","author":"Salentin","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Bowers, K.J., Chow, 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 ACM\/IEEE Conference Supercomputing (SC06), Tampa, FL, USA.","DOI":"10.1109\/SC.2006.54"},{"key":"ref_67","unstructured":"Bergdorf, M., Baxter, S., Rendleman, C.A., and Shae, D.E. (2016). Desmond\/GPU Performance as of November 2016, D. E. Shaw Research Technical Report. DESERS\/TR-2016-01."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"4291","DOI":"10.1021\/acs.jctc.1c00302","article-title":"OPLS4: Improving force field accuracy on challenging regimes of chemical space","volume":"17","author":"Lu","year":"2021","journal-title":"J. Chem. Theory Comput."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1002\/jcc.21372","article-title":"Fast and accurate predictions of binding free energies using MM-PBSA and MM-GBSA","volume":"31","author":"Rastelli","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1021\/ci100275a","article-title":"Assessing the performance of the MM\/PBSA and MM\/GBSA methods. 1. The accuracy of binding free energy calculations on molecular dynamics simulations","volume":"51","author":"Hou","year":"2011","journal-title":"J. Chem. Inf. Model."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s13321-018-0283-x","article-title":"ADMETlab: A platform for systematic ADMET evaluation based on a comprehensively collected ADMET database","volume":"10","author":"Dong","year":"2018","journal-title":"J Cheminform."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"W5","DOI":"10.1093\/nar\/gkab255","article-title":"ADMETlab 2.0: An integrated online platform for accurate and comprehensive predictions of ADMET properties","volume":"49","author":"Xiong","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/978-1-4939-8760-3_12","article-title":"Use of surface plasmon resonance (SPR) to determine binding affinities and kinetic parameters between components important in fusion machinery","volume":"1860","author":"Sparks","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1016\/j.bios.2004.04.017","article-title":"Characterization of a self-assembled monolayer of thiol on a gold surface and the fabrication of a biosensor chip on surface plasmon resonance for detecting anti-GAD antibody","volume":"20","author":"Lee","year":"2005","journal-title":"Biosens. Bioelectron."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"160696","DOI":"10.1098\/rsos.160696","article-title":"Thioflavin T as an amyloid dye: Fibril quantification, optimal concentration effect on aggregation","volume":"4","author":"Xue","year":"2017","journal-title":"R. Soc. Open Sci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.sbi.2019.04.001","article-title":"The role of circular dichroism spectroscopy in the era of integrative structural biology","volume":"58","author":"Wallace","year":"2019","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_77","first-page":"E3095","article-title":"Accurate secondary structure prediction and fold recognition for circular dichroism spectroscopy","volume":"11","author":"Micsonai","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/978-1-0716-0892-0_11","article-title":"BeStSel: From secondary structure analysis to protein fold prediction by circular dichroism spectroscopy","volume":"Volume 2199","author":"Chen","year":"2021","journal-title":"Structural Genomics, Methods"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"5687","DOI":"10.1046\/j.1432-1327.2000.01658.x","article-title":"Cytoprotective antioxidative function of tyrosine and tryptophan residues in transmembrane proteins","volume":"267","author":"Moosmann","year":"2000","journal-title":"Eur. J. Biochem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1515\/jcim-2015-0051","article-title":"Evaluation of the antioxidant properties of tryptophan and its metabolites in in vitro assay","volume":"13","author":"Nayak","year":"2016","journal-title":"J. Complement. Integr. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"135481","DOI":"10.1016\/j.foodchem.2023.135481","article-title":"Enrichment of antiplatelet peptides and removal of fishy odor from silver carp skin collagen hydrolysates by macroporous resins: pH value of loading sample affects the peptides separation","volume":"411","author":"Cui","year":"2023","journal-title":"Food Chem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"5.8.1","DOI":"10.1002\/0471250953.bi0508s52","article-title":"Protein structure and functionalization prediction using I-Tasser","volume":"52","author":"Yang","year":"2015","journal-title":"Curr. Protoc. Bioinformatics."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"6233","DOI":"10.1021\/acs.jpcb.4c00664","article-title":"Exploring the application of SiteMap and SiteFinder for focused cryptic pocket identification","volume":"128","author":"Ge","year":"2024","journal-title":"J. Phys. Chem. B"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/35081564","article-title":"Alpha-synuclein and neurodegenerative diseases","volume":"2","author":"Goedert","year":"2001","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"de Groot, N., Pallar\u00e9s, I., Avil\u00e9s, F., Vendrell, J., and Ventura, S. (2005). Prediction of \u201chot spots\u201d of aggregation in disease-linked polypeptides. BMC Struct. Biol., 5.","DOI":"10.1186\/1472-6807-5-18"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2750","DOI":"10.1038\/s41467-024-46832-5","article-title":"Structure of alpha-synuclein fibrils derived from Lewy body dementia tissue","volume":"15","author":"Dhavale","year":"2024","journal-title":"Nature Commun."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2521","DOI":"10.1021\/acschemneuro.8b00177","article-title":"Alpha Synuclein Fibrils Contain Multiple Binding Sites for Small Molecules","volume":"9","author":"Hsieh","year":"2018","journal-title":"ACS Chem. Neurosci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.parkreldis.2021.06.023","article-title":"A new alpha-synuclein missense variant (Thr72Met) in two turkish families with Parkinsons disease","volume":"89","author":"Fevga","year":"2021","journal-title":"Park. Relat. Disord."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2646","DOI":"10.1021\/acschemneuro.2c00327","article-title":"Threonine cavities are targetable motifs that control alpha-synuclein fibril growth","volume":"13","author":"Kochen","year":"2022","journal-title":"ACS Chem. Neurosci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/s41594-020-0384-x","article-title":"A short motif in the N-terminal region of \u03b1-synuclein is critical for both aggregation and function","volume":"27","author":"Doherty","year":"2020","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1074\/jbc.M008919200","article-title":"A hydrophobic stretch of 12 amino acid residues in the middle of \u03b1-synuclein is essential for filament assembly","volume":"276","author":"Giasson","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1096\/fj.03-1346fje","article-title":"A strategy for designing inhibitors of \u03b1-synuclein aggregation and toxicity as a novel treatment for Parkinson\u2019s disease and related disorders","volume":"18","author":"Paleologou","year":"2004","journal-title":"FASEB J."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/nature15368","article-title":"Structure of the toxic core of \u03b1-synuclein from invisible crystals","volume":"535","author":"Rodriguez","year":"2015","journal-title":"Nature"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"3338","DOI":"10.1523\/JNEUROSCI.0285-07.2007","article-title":"Aggregated alpha-synuclein mediates dopaminergic neurotoxicity in vivo","volume":"27","author":"Periquet","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"8870","DOI":"10.1021\/bi034028+","article-title":"A peptide motif consisting of glycine; alanine; and valine is required for the fibrillization and cytotoxicity of human alpha-synuclein","volume":"42","author":"Du","year":"2003","journal-title":"Biochemistry"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Lashuel, H. (2020). Do Lewy bodies contain alpha-synuclein fibrils? And does it matter? A brief history and critical analysis of recent reports. Neurobiol. Dis., 141.","DOI":"10.1016\/j.nbd.2020.104876"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"15","DOI":"10.14802\/jmd.23213","article-title":"Ultrastructures of \u03b1-synuclein filaments in synucleinopathy brains and experimental models","volume":"17","author":"Tarutani","year":"2024","journal-title":"J. Mov. Disord."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"29","DOI":"10.4103\/1735-1995.181989","article-title":"Alpha-Synuclein structure, functions and interactions","volume":"21","author":"Nouri","year":"2016","journal-title":"J. Res. Med. Sci."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.bbamem.2011.07.032","article-title":"Biophysics of \u03b1-synuclein membrane interactions Biochim","volume":"1818","author":"Pfefferkorn","year":"2012","journal-title":"Biophys. Acta."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"15313","DOI":"10.1074\/jbc.M213128200","article-title":"A broken \u03b1-helix in folded \u03b1-synuclein","volume":"278","author":"Chandra","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"118901","DOI":"10.1016\/j.molliq.2022.118901","article-title":"Molecular dynamics simulation approach for discovering potential inhibitors againsts SARS-CoV-2: A structural review","volume":"354","author":"Ghahremanian","year":"2022","journal-title":"J. Mol. Liq."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Asare, I., Galende, A., Garcia, A., Cruz, M., Moura, A., Campbell, C., Scheyer, M., Alao, J., Alston, S., and Kravats, A.N. (2022). Investigating structural dynamics of KCNE3 in different membrane using molecular dynamics simulations. Membranes, 12.","DOI":"10.3390\/membranes12050469"},{"key":"ref_103","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_104","doi-asserted-by":"crossref","unstructured":"Honarmand, S., Dabirmanesh, B., Amanlou, M., and Khajeh, K. (2019). The interaction of several herbal extracts with \u03b1-synuclein: Fibril formation and surface plasmon resonance analysis. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0217801"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Sulatskaya, A.I., Rodina, N.P., Sulatsky, M.I., Povarova, O.I., Antifeeva, I.A., Kuznetsova, I.M., and Turoverov, K.K. (2018). Investigation of \u03b1-Synuclein in amyloid fibrils using the fluorescent probe Thioflavin-T. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19092486"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"W90","DOI":"10.1093\/nar\/gkac345","article-title":"BeStSel: Webserver for secondary structure and fold prediction for protein CD spectroscopy","volume":"50","author":"Micosonai","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2813","DOI":"10.1021\/acschemneuro.2c00180","article-title":"Nanoscale characterization of parallel and antiparallel \u03b2-sheet amyloid beta 1\u201342 aggregates","volume":"13","author":"Zhaliazka","year":"2022","journal-title":"ACS Chem. Neurosci."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Baliyan, S., Mukherjee, R., Priyadarshini, A., Vibhuti, A., Gupta, A., Pandey, R., and Chang, C.-M. (2022). Determination of antioxidants by DPPH radical scavenging activity and quantitative photochemical analysis of Ficus Relgiosa. Molecules, 27.","DOI":"10.3390\/molecules27041326"},{"key":"ref_109","first-page":"9.12.1","article-title":"Overview on the Rule of Five","volume":"49","author":"Pollastri","year":"2010","journal-title":"Curr. Prot. Pharmarcol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"277","DOI":"10.2174\/1568026013395100","article-title":"Physiochemical Profiling (Solubility; Permeability; and Charge State)","volume":"1","author":"Avdeef","year":"2001","journal-title":"Curr. Topics Med. Chem."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1021\/tx800035b","article-title":"hERG Potassium Channels and the Structural Basis of Drug-Induced Arrythmias","volume":"21","author":"Mitcheson","year":"2008","journal-title":"Chem. Res. Toxicol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1007\/s40262-020-00867-1","article-title":"Effect of P-glycoprotein (P-gp) inducers on exposure of P-gp substrates: Review of clinical drug-drug interaction studies","volume":"59","author":"Elmeliegy","year":"2020","journal-title":"Clin. Pharmacokin."}],"container-title":["Biomimetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2313-7673\/9\/11\/705\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:34:10Z","timestamp":1760114050000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2313-7673\/9\/11\/705"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,18]]},"references-count":112,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["biomimetics9110705"],"URL":"https:\/\/doi.org\/10.3390\/biomimetics9110705","relation":{},"ISSN":["2313-7673"],"issn-type":[{"type":"electronic","value":"2313-7673"}],"subject":[],"published":{"date-parts":[[2024,11,18]]}}}