Biophysics: Studying Single Biological Molecules with Atomic-Scale Resolution
Physical Measurement Laboratory, Quantum Physics Division
Please note: This Agency only participates in the February and August reviews.
Single molecule studies are revolutionizing biophysics. The Perkins group focuses on developing and applying high-precision single-molecule studies based on optical traps and atomic force microscopes to answer fundamental biophysical questions, including: how do motor proteins transduce chemical energy into mechanical motion and what are the energetics and dynamics underling membrane proteins folding? Specifically, we developed an optical-trapping assay with Ångström-scale stability and resolution in all three dimensions and are applying these high resolution studies to DNA-based molecular motors and RNA-folding. In a parallel effort, we significantly enhanced the biophysical capabilities of an atomic force microscope (AFM). Specifically, we achieved sub-pN force precision and stability over a broad timescale (0.1-100 s) for the first time; and, most recently, improved the timescale of sub-pN precision of AFM by another factor of 50. We are currently applying these improvements to mechanically unfolding and refolding interesting biological molecules with 1-µs resolution, including membrane protein as well as continuing to pursue further metrological improvements in single molecule studies.