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These LBs harbor various proteins, prominently including \u03b1\u2010Synuclein (Syn) aggregates, implicated in disease pathology. A promising avenue in PD treatment involves targeting Syn aggregation. Recent findings from our research have shown that 3,4\u2010dihydroxyphenylacetic acid (DOPAC) and 3,4\u2010dihydroxyphenylethanol (DOPET) possess the ability to impede the formation of Syn fibrils by disrupting the aggregation process. Notably, these compounds primarily engage in noncovalent interactions with the protein, leading to the formation of off\u2010pathway oligomers that deter fibril growth. Through proteolysis studies and mass spectrometry (MS) analysis, we have identified potential covalent modifications of Syn in the presence of DOPAC, although the exact site remains elusive. Employing molecular dynamics simulations, we delved into how DOPAC\u2010induced covalent alterations might affect the mechanism of Syn aggregation. Our findings indicate that the addition of a covalent adduct on certain residues enhances fibril flexibility without compromising its secondary structure stability. Furthermore, in the monomeric state, the modified residue fosters novel bonding interactions, thereby influencing long\u2010range interactions between the N\u2010 and C\u2010termini of the protein.<\/jats:p>","DOI":"10.1002\/biof.2086","type":"journal-article","created":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T10:04:50Z","timestamp":1716804290000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Catechol\u2010induced covalent modifications modulate the aggregation tendency of \u03b1\u2010synuclein: An in\u2010solution and in\u2010silico study"],"prefix":"10.1002","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3216-6071","authenticated-orcid":false,"given":"Ilenia","family":"Inciardi","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences University of Padova  Padova 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