THE Operational and design principles of molecular machines

High-resolution time-dependent single-molecule spectroscopic techniques have been developed to quantitatively address the functional consequences of structural fluctuations in macromolecules. While we continue to develop new methods to advance the state of the art, the already-developed techniques are being applied to examine several biological macromolecules of health and technological interest.

Instrumentation and Technology Development

Photon-by-Photon Single-Molecule Analysis is a practice developed by our group that, experimentally, records the arrival time of each detected photon and, theoretically, analyzes the photon time series using data-driven and model-free methods that are statistically robust. The change-point analysis is one such method developed by our group. Additional new methods are currently under development.

Adenylate Kinase

Adenylate kinase is an ubiquitous enzyme that maintains the energy balance in cells. It has been one of the prototypical model system for studying protein dynamics. Conformational gating and dynamically induced fit are two operational principles observed from our single-molecule experiments (PNAS 2007).

Protein Tyrosine Phosphatase B

Protein Tyrosine Phosphatase B from Micobaterium tuberculosis is a protein that has been implicated in the vidulence of tuberculosis. Our single-molecule study revealed that the largge-amplitude conformational movements protect the active site from being oxidized and at the same time allow its interactions with substrates. More generally, our work provides the first experimental evidence that local folding / unfolding directly impacts on the kinetics of conformational changes (JACS 2010).

Human Insulin Degrading Enzyme

The human insulin degrading enzyme digests insulin and the Aβ peptide, and has implications in type-II diabetes and Alzheimer's disease, respectively. Working with Prof. Wei-Jen Tang of the University of Chicago, we are currently using high-resolution single-molecule spectroscopy to gain a better understanding for the operation principles of this remarkable protein.

Other collaborators include:

Jhih-Wei Chu

Professor, Department of Biological Science and Technology & Institute of Bioinformatics and Systems Biology
National Chiao Tung University, Taiwan