Introduction

A major stumbling block in developing a first principles understanding of crystal nucleation is the lack of a detailed understanding of the forces that exist between protein molecules in solution. Proteins are complex molecules whose surfaces consist of amino acid residues that possess charged and uncharged regions and in general have complicated interactions with the surrounding electrolyte. The forces between protein molecules in solution include, for example, screened repulsive Coulomb interactions and attractive van der Waals interactions. In addition, protein–ion dispersion forces and hydrophobic and hydration forces play an important role. To further complicate matters, subtle mutations on the surface of these molecules (e.g. sickle hemoglobin, gamma crystallin) can have profound effects on their intermolecular interactions. One can imagine, therefore, how difficult it is, in principle, to determine a realistic model of protein–protein interactions. Progress to date has been based on rather simple models which are spatially isotropic, with short range attractive interactions. Clearly, more realistic models are needed to obtain a more quantitative understanding of the protein phase diagram, nucleation rate, and subsequent growth. One important aspect of the interactions between globular protein molecules, which is only recently being considered by theorists, is that many of the interactions are highly directional.