Interaction Volume Is a Measure of the Aggregation Propensity of Amyloid-β

This study highlights the significance of the partial molar volume of amino acids in predicting the aggregation propensity of an intrinsically disordered protein, amyloid-β (Aβ), and its mutants in aqueous solution. The change in the interaction volume of the protein or mutant is quantitatively correlated with its calculated experimental aggregation propensity. This method also reveals how the interaction volume may be tuned by changing the charge and hydrophobicity of Aβ. While a positive change in the interaction volume and a higher aggregation propensity are observed for mutants with a decrease in the overall charge and/or an increase in hydrophobicity, a reverse trend is observed for the mutants with a decrease in the hydrophobicity and/or an increase in its charge. Hence, the interaction volume may be considered as a key parameter for monitoring protein aggregation that bridges the gap between the experimental aggregation kinetics and solvation thermodynamics.