Research interests (click topic for more information)
We are interested in the way the structure of motor proteins constrains their biological function.
Our recent focus has been on Myosin V, a two-headed motor protein that transports cellular cargo
by walking hand-over-hand on actin filaments. We developed an analytically solvable theory capturing
the rich variety of myosin stepping dynamics, quantitatively matching single-molecule experimental data.
The theory explores the design space of the motor, predicting that its function is robust against small perturbations to its chemical cycle and
the architecture of its lever arms.
A movie illustrating the relaxation of the myosin lever arms after one head detaches, and their stochastic fluctuations during the search for the target binding
site on actin.
The precision and stability of optical tweezers have given us tantalizing glimpses of individual proteins
folding and unfolding under force. However the theory relating what is observed in the lab—the displacements of
optically trapped beads—and the actual conformational changes of the protein, is still incomplete.
The methods we have developed allow experimentalists to reliably extract two intrinsic aspects of
the protein from the measured data:
2. The free energy landscape along the end-to-end extension of the protein. Our approach is based on
direct physical modeling of the entire tweezer apparatus, and
has been extensively verified by numerical simulations.