Flourescent Biomarkers for Amyloid Fibrils

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Luminescent conjugated oligothiophenes are highl y promising candidates for biomarkers for amyloid misfolds and thereby for early-stage detection of neurodegenerative diseases such as Alzheimer’s and Parkinson's disease. The elucidation of the microscopic mechanism and design principles behind these biomarkers requires theoreticalassi stance. Finding suitable theoretical models that allow sufficiently accurate spectra calculations for such large, dynamic, and complex biomolecular systems is a highly challenging task. There is, hence, a great need for efficient and adaptive theoretical models capable of incorporating the essential factors in spectra calculationof biomolecular systems sufficiently accurately.
We aim at combining the advantages of different state-of-the-art computational methods and thereby to devise an efficient and adaptable methodology for assisting the interpretation of existing spectra and predicting the performance of new candidates for biomarkers with respect to spectral discrimination of amyloid protein misfolds and thereby for improved early-stage detection and more nuanced diagnosis of diseases such as Alzheimer’s and Parkinson’s disease.

As a first step to this goal, we have performed large-scale non-biased molecular dynamics simulations of an amyloid fibril in the presence of luminescent biomarkers. In these simulations, we succeeded in finding a convincing binding site for a luminescent oligothiophene biomarkers, which is in agreement with current experimental results.

C König, R Skånberg, I Hotz, A Ynnerman, P Norman, and M Linares, Binding Sites for Luminescent Amyloid Biomarkers from non-Biased Molecular Dynamics Simulations, Chem. Commun., 54, 3030-3033 (2018).