One of the biggest scientific problems of the past 50 years is how a protein folds into a stable 3-dimensional conformation critical for its function in the cell. While the process should be predictable from just the sequence of amino acids, one is still unable to make such a prediction. The most successful models of protein folding have been simple two- or three-state models. However, recent results from the PI's lab as well as others have shown these simple models to fail when examining fast folding kinetics in a variety of systems. The objective of this project is to further these preliminary studies by investigating different aspects of complexity in folding proteins using a variety of spectroscopic probes and state-of-the-art ultrarapid mixers. The experimental results will be compared with simulation results from various computational biology labs. The long-term goal of this research is to develop a theory which can predict the process solely from the amino acid sequence. By coupling theory and experiment on the microsecond timescale and considering the impact of complexity, this project will significantly advance the field of protein folding towards the long-term goal.
Broader Impacts: This project encompasses aspects of structural biology, computation biology, optical spectroscopy and polymer physics. Therefore the students involved in this work will require cross-disciplinary training to accomplish the scientific goals. As part of a new graduate program in Quantitative Biology at MSU, the PI has designed new lecture and laboratory courses to introduce physical science students to biology and biology students to quantitative methods. These courses continue to evolve and the PI will also develop a course aimed at undergraduates in the life sciences to take a more quantitative approach to biology.
