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The acidic C-terminal tails of tubulin, known as E-hooks, play a central role in regulating interactions between microtubules and motor proteins, microtubule-associated proteins, and enzymatic modifiers. Despite their functional importance, the intrinsic structural properties of these peptide segments remain poorly characterized due to their intrinsically disordered nature. In this work, we present quantum-mechanically optimized structures of hexamer peptides derived from \u03b2-tubulin E-hook sequences. Density functional theory calculations were used to optimize peptide geometries using progressively larger basis sets. From the optimized geometries we calculated theoretical Raman spectra, Ramachandran backbone dihedral distributions, and measured radii of gyration to resolve composition dependent structural tendencies. The combined Raman and conformational analyses provide a systematic computational approach for comparing simulated and experimental Raman spectra of tubulin E-hooks and other intrinsically disordered proteins and offer insight into how E-hooks contribute to the recognition mechanisms underlying the tubulin code.<\/jats:p>","DOI":"10.64898\/2026.08.11.744204","type":"posted-content","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T12:40:16Z","timestamp":1786538416000},"source":"Crossref","is-referenced-by-count":0,"title":["Tubulin E-hook Hexamers Reveal Charge Dependent Compaction and Transient Secondary Structure Signatures"],"prefix":"10.64898","author":[{"given":"Alexander C.","family":"Bromley","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, University of Mississippi, University, MS 38677 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas A.","family":"Kruse","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Mississippi, University, MS 38677 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connor R.","family":"Brower","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Mississippi, University, MS 38677 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madison K.","family":"Beam","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Mississippi, University, MS 38677 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan I.","family":"Hammer","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Mississippi, University, MS 38677 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan C.","family":"Fortenberry","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Mississippi, University, MS 38677 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3516-3948","authenticated-orcid":false,"given":"Dana N.","family":"Reinemann","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Mississippi, University, MS 38677 USA"},{"name":"Department of Chemical Engineering, University of Mississippi, University, MS 38677 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026081312250646000_2026.08.11.744204v1.1","doi-asserted-by":"crossref","unstructured":"McIntosh, J.R. , E.L. 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