Calculation of phase diagrams for aqueous protein solutions

In recent publications, phase diagrams have been generated from simple mode ls of globular proteins interacting via anisotropic interactions. In these models, protein solubility is determined from the favorable energetic inter actions due to the formation of protein-protein contacts in the crystal tha t overcome the unfavorable loss in entropy from constraining a protein mole cule upon crystallization. In this work, we develop a statistical mechanica l description for protein crystallization of which a key component is the q uantitative calculation of this entropy loss. We calculate the entropic ter m from experimental crystallographic data for lysozyme and show that the em pirical correlation of the osmotic second virial coefficient with lysozyme solubility corresponds to 6-8 contacts per protein molecule in the crystal. In addition, our model predicts that the two-body potential of mean force between lysozyme molecules is highly anisotropic. This has important implic ations for determining the position of a fluid-fluid critical point metasta ble to the fluid-solid equilibrium. That position is important because, as shown previously, crystallization kinetics are maximized at temperatures sl ightly exceeding the fluid-fluid critical temperature.