Our goal is to develop a toolkit to extract important quantitative parameters that control the folding and dynamics of proteins and nucleic acids, as well as protein-nucleic acid interactions at the single-molecule level.
My current research focuses on the theory of single-molecule fluorescence measurements. Researchers can use single-molecule Förster resonance energy transfer (FRET) between fluorescent donor and acceptor labels attached to a protein or nucleic acid to probe a molecule’s structure, dynamics, and function. The output of these experiments is a sequence of photons of different colors (some emitted by the donor and some by the acceptor) separated by apparently random time intervals. Quantitative analysis of photon sequences requires complete understanding of the complex microscopic processes involved. We have developed a rigorous theoretical framework for the analysis of such single-molecule FRET experiments. The theory describes how conformational dynamics, diffusion of the molecule through the laser spot, shot noise, dye photophysics, and other factors influence photon statistics. Scientists in the Laboratory of Chemical Physics at the NIDDK now routinely use these methods to analyze single-molecule experiments on protein folding.