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Binding sites for luminescent amyloid biomarkers from non-biased molecular dynamics simulations
Carolin König1, Robin Skånberg2, Ingrid Hotz2
1Department of Theoretical Chemistry and Biology, KTH Royal Institute of Technology, Roslagstullsbacken 15, SE-106 91 Stockholm, Sweden. linares@kth.se.
Abstract:
A very stable binding site for the interaction between a pentameric oligothiophene and an amyloid-β(1-42) fibril has been identified by means of non-biased molecular dynamics simulations. In this site, the probe is locked in an all-trans conformation with a Coulombic binding energy of 1200 kJ mol-1 due to the interactions between the anionic carboxyl groups of the probe and the cationic ε-amino groups in the lysine side chain. Upon binding, the conformationally restricted probes show a pronounced increase in molecular planarity. This is in line with the observed changes in luminescence properties that serve as the foundation for their use as biomarkers.
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