Figure 5.

(a) Probability of naproxen molecule binding to Aβ dimer, $P_b\left(T\right)$, as a function of temperature. Binding temperature T_b is associated with the midpoint of $P_b\left(T\right)$. Inset shows the number of naproxen ligands bound to Aβ dimer $\langle L\rangle$ (continuous line) and the number of ligands bound to Aβ aggregation interface $\langle L_i\rangle$ (dashed line) versus temperature. (b) Free energy $F\left(r_b\right)$ of naproxen as a function of the distance between ligand and Aβ dimer, r_b (solid circles). The free energy of binding $\Delta F_b$ is computed by integrating over the ligand bound states with $F\left(r_b\right)\le F_{\text{min}}+1.0RT$, where F_min is the minimum in $F\left(r_b\right)$. The values of F at $r_b>29$ Å are set to zero and correspond to unbound state. Free energies $F\left(r_b\right)$ describing naproxen binding to Aβ monomer and fibril computed earlier (35) are given by open circles and squares, respectively. Inset: Radial distribution functions, $g_{pp}\left(r\right)$ and $g_{lp}\left(r\right)$, map minimum distances between amino acids from different peptides and between ligands and amino acids, respectively. The functions $g_{pp}\left(r\right)$ obtained in water and naproxen solution are shown by continuous gray and black lines; the function $g_{lp}\left(r\right)$ is represented by a dashed line. All plots in (b) are obtained at 360 K. The figure implies that naproxen binds to Aβ dimer and interferes with interpeptide interactions.