Molecular Modeling for Protein Aggregation and Formulation

This chapter overviews protein aggregation pathways followed by a discussion of protein interactions with cosolvents and then protein?protein interactions. It covers the recent developments in the understanding of protein interactions with salts, and to a much lesser extent, with other excipients such as sugars, glycerol, or amino acids. Understanding how protein?cosolvent interactions impact upon protein?protein interactions is only possible by using simplistic descriptions of proteins, such as Deryaguin, Landau, Verwey, and Overbeek (DLVO) theory. A simulation study on the pair potential of mean force for either methane or neopentane in salt solutions found that the ion specific effects correlated well with the effect of salt on the hydrogen bonding network in bulk water. The interactions of salt ions and protein charged groups are best rationalized in terms of the law of matching water affinities (LMWA).