Fig. 6.

Direct protein–protein interactions and the water-mediated attraction responsible for the compact dimer formation. (A) Presence (indicated by vertical bars) of intermonomer hydrogen bonds, (B) the intermonomer van der Waals interaction energy, and (C) the solvation entropy component -TδΔs of the PMF plotted as a function of time. In these panels, time regimes where intermonomer heavy atom contacts are present (see Fig. 1B) are colored by light green. In A, A(X)-B(Y) indicates that atom X in residue A of monomer 1 makes a hydrogen bond with atom Y in residue B of monomer 2. (D) Aβ42 dimer structures at 47, 53, 76, and 100 ns with surrounding water molecules. Two monomers are colored by yellow and cyan, respectively, and those residues that are to make intermonomer heavy atom contacts at 100 ns are shown in sphere representation. Water molecules are drawn in stick representation (O: red, H: white). Direct protein–protein interactions lead to the formation of intermonomer hydrogen bonds and van der Waals contacts. Concomitant dehydration of interfacial water gives rise to a water-mediated attraction of entropic origin quantified by -TδΔs. These favorable changes in the protein internal energy and the solvation entropy prompt the formation of compact dimer structure.