Protein Folding, Binding and Aggregation in the Cell: Role of Stochastic Resonance

Understanding how proteins fold and form multi-protein assemblies inside the cell is an important fundamental problem that has vital implications for development of therapeutic methods. The cellular environment is critically different from the dilute and static conditions under which proteins are usually studied in vitro or using computational approaches. Protein folding and protein-protein binding inside the cell occur in highly crowded and fluctuating environment, which is critical for stability of larger proteins and assemblies. While, the role of crowding has been extensively investigated previously, the role of fluctuations has been largely neglected. Here, we report on our investigation into the role of local fluctuations that can be attributed to fluctuations of the chemical environment around the protein inside the cell. Using coarse-grained molecular simulations we establish that such fluctuations can have a substantial effect when the characteristic frequency of the applied fluctuations coincides with the “native” rates of the reaction, consistent with the phenomenon of stochastic resonance observed in many other condensed-matter processes. Our computational and theoretical findings as well as the recent experimental conformation of our results will be presented.