Biophysics: Studying Single Biological Molecules with Atomic-Scale Resolution
Physical Measurement Laboratory, Quantum Physics Division
NIST 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.