Structure formation of peptides in the PRIME20 model

A. Böker and W. Paul

Martin-Luther-Universität Halle-Wittenberg, 06099 Halle

The relation between conformations of a polypeptide is governed by local minima in the free energy function. Coarse-grained models tend to simplify the free energy in such a way that these local minima are ignored. To circumvent this problem, the level of coarse graining needs to be chosen appropriately. PRIME20 [1] provides reasonable detail by mapping each amino acid to four beads, but keeps parameter space simple with the set of interactions reduced to 19 energy parameters.
Poly-Glutamines (polyQ) are associated with Huntington’s disease due to their ability to aggregate into an amyloid state. Single polyQ chains have been found to form a beta hairpin as a precursor to these aggregates. We will discuss the temperature dependent end-to-end distance of the chains in relation to TTET and FRET experiments performed on polyQ chains.
We perform thermodynamic simulations of single PRIME20 chains using the “SAMC” [2] variation of Wang-Landau Monte Carlo sampling which provides insight in different statistical ensembles at the expense of dynamic information. The aforementioned polyQ are compared to poly-Alanines with a lower tendency to form beta structure motifs.

[1] M. Cheon, I. Chang, C. K. Hall, Proteins, 78, 2950 (2010) (link)
[2] B. Werlich, T. Shakirov, M. P. Taylor, W. Paul, Comp. Phys. Comm., 186, 65 (2015) (link)