Thermodynamic phase diagram of amyloid-β (16–22) peptide

Significance Phase diagrams of atomic systems are calculated routinely by computer simulations, but such calculations are absent for even the simplest peptides. Previous simulations are mainly nonequilibrium and focus on the assembly of peptides from the monomeric state to the aggregated state. To obtain accurate equilibrium solubilities, it is necessary to simulate many assembly and disassembly events of fibrillar aggregates, which is notoriously difficult as it requires breaking many hydrogen bonds. We overcome these challenges and calculate the equilibrium phase diagram of amyloid β protein (16–22) (Aβ 16–22 ), the archetypal amyloid former, using a realistic protein model. Importantly, our prediction of Aβ 16–22 solubility over temperatures from 277 to 330 K agrees well with experimental measurements.