(184o) Additives for Inhibiting Protein Aggregation: Mechanistic Understanding, Rational Design, and Performance Prediction

Protein solutions degrade mainly due to aggregation, which not only makes it difficult to store them at high concentrations for long periods of time but also reduces their biological activity. One of the ways to counter aggregation is to control the protein environment by adding additives to the aqueous protein solutions. Various additives have been shown to lower aggregation rate e.g. sugars, polyols (polyethylene glycol) etc. The exact mechanism by which these additives inhibit aggregation is not clear. Therefore, rational design of anti-aggregation additives is not possible. Selection of additives is therefore done using a heuristic, experimental screening procedure. In this work, a computational study is performed to (a) understand the mechanism by which arginine, a widely used aggregation suppressor inhibits protein aggregation, (b) design new additives based on the acquired understanding of the arginine mechanism, and (c) predict the effect of additives on the free energy of protein aggregation using small peptides as model systems.