(259d) Using Molecular Simulation to Explore the Phase Behavior of a Simple Model Protein

Many neurological diseases, cataracts, and sickle-cell diseases are linked to protein phase separation and aggregation. At the heart of these phenomena are protein-protein interactions. It is known that these interactions are influenced by numerous physiological factors such as salt concentration, pH, and temperature. Modest variation of any of these factors can lead to significant changes in protein phase stability and behavior. For example, George and Wilson¹ have found that there exists a small range of protein-protein attraction leading to crystallization. It has also been found by ten Wolde and Frenkel² that protein crystallization and nucleation may be enhanced by liquid-liquid phase separation. In this work, we take steps to better understand the relationship between the macroscopic phase behavior of a protein solution and its underlying microscopic interactions by studying a simple model for lysozyme introduced by Carlsson et al.³ The model describes lysozyme as a spherical protein with a hard core, a single spherically-symmetric hydrophobic interaction, and a collection of embedded charge residues. Charge locations are based on information from the protein data bank and the charge values are pH dependent. We will present results that indicate how protein phase behavior evolves with solution conditions based on grand canonical transition matrix Mote Carlo simulations.

¹ A. George and W. W. Wilson, Acta Crystallographica Section D-Biological Crystallography 50, 361 (1994). ² P. R. tenWolde and D. Frenkel, Science 277 (5334), 1975 (1997). ³ F. Carlsson, M. Malmsten, and P. Linse, Journal of Physical Chemistry B 105 (48), 12189 (2001).