Title : Role of Protectants and Denaturants in Polymers and Proteins: Insights from Computer Simulation



Longstanding mechanistic questions about the role of protectant Trimethylamine N- oxide (TMAO) which favors protein folding and the denaturant Urea are addressed by studying their effects on the folding of a model polymer chain. Using atomistic molecular dynamics simulations, we show that TMAO and Urea solutions act dramatically differently on these model polymer chains. Their behaviors are sensitive to the strength of the attractive dispersion interactions of the chain with its environment: when these dispersion interactions are high enough, TMAO suppresses the formation of extended conformations of the model polymer as compared to water, while urea promotes formation of extended conformations. Similar trends are observed experimentally on real protein systems. Quite surprisingly, we find that both protectants and denaturants strongly interact with the model polymer, seemingly in contrast with existing explanations of the effect on proteins. We show that what really matters for a protectant is its effective depletion as the polymer conformation changes, which leads to a negative change in the preferential binding coefficient, while the reverse is true in case of denaturant. Finally, we show our results on a simple model polymer is in reasonable agreement with a recent single molecule experiment on a synthetic polymer called polystyrene