(24a) Self-Assembly, Phase Separation, and Unfolding of Coarse-Grained Proteins in Solution

Understanding the factors that impact the stability of native-state proteins and induce either native or non-native protein aggregation processes in solution is a challenge of great practical and technological importance. Protein aggregation has been linked to numerous human pathologies such as Alzheimer's and Huntington's diseases. It also leads to premature degradation of pharmaceutical formulations, severely restricting the available strategies for purification, storage, and delivery of therapeutic drugs. In this talk, we discuss simulations of a globular protein solutions using a recently developed coarse-grained modeling strategy [1,2]. The simulations employ a novel implementation of transition matrix Monte Carlo techniques introduced earlier (see, e.g., [3]) to probe how the anisotropy of the hydrophobic units on the surface of the proteins affect native-state stability, protein-protein interactions, self-assembly, and phase separation in solution.

[1] J. K. Cheung and T. M. Truskett, Biophys. J. 89, 2372-2384 (2005).

[2] V. K. Shen, J. K. Cheung, J. R. Errington, and T. M. Truskett, Biophys. J. 90, 1949-1960 (2006).

[3] V. K. Shen and J. R. Errington, J. Chem. Phys. 122, 064508 (2005).