Daniel Nilsson
Macromolecular Crowding as a Determinant of Protein Viability -- a Lattice Model Study

Master Thesis in Theoretical Physics

Abstract: We study the effects of macromolecular crowding with interacting crowders in the simple HP-model of protein folding, by performing Monte Carlo simulations of a single flexible HP protein in the presence of folded rigid crowders. In contrast to the well-known stabilization of steric crowders, we find that interacting crowders usually destabilize the test protein, often significantly so. As such, careful design of the crowder surfaces is necessary, and we find that the size and geometry of single hydrophobic patches are more important than the total amount of hydrophobicity on crowder surfaces. In addition, test proteins are found to be more stable if they have fewer native contacts between hydrophobic and polar residues. We also investigate the effects of crowding on evolutionary processes, finding that incorporating constraints based on crowding noticeably affects the type of fold-switches that are allowed. Finally, the effects of crowding on binding and aggregation were investigated. In "realistic" situations we find that crowding weakly destabilizes both processes.


LU TP 17-05