UC Merced

Proteins act as cellular nanomachines by carrying out a wide variety of functions, enabling life as we know it today. They exist in a dynamic equilibrium between various structural conformations ranging from their functional native structure to the nascent unfolded chain. The diversity of the protein structures qualifies proteins for carrying out diverse functions. Protein conformational dynamics play a key role in functional control, as it is the dynamic equilibrium between different conformations under cellular conditions that enables the regulation of functionalities. Single-molecule FRET experiments combined with maximum likelihood analysis (MLA) offer a unique opportunity for experimentalists to determine various parameters involved in the folding dynamics which were previously accessible only through simulations. All details about conformational dynamics happening in the protein within the interphoton time is embedded in the single-molecule photon trajectory and the MLA method has the potential to extract these details with the limitation being the model being used to describe folding. Traditional models used to describe protein folding are simple kinetic models with inherent assumptions about the nature of the folding. While the simplicity of these models makes them an attractive approach, they come with serious limitations in resolving the dynamics. Here, we demonstrate a free energy surface-based approach to extract and dissect various dynamic processes happening along protein folding reactions. Everything that living things do can be understood in terms of the jiggling and wiggling of atoms.” – Richard Feynman Through this dissertation, we are trying to gain a better understanding of the jiggling and wiggling of protein chain as it (un)folds along a one-dimensional free energy surface.