Download Faraday Discussion Meeting September 2002

SINGLE MOLECULE MECHANICS: EXPLORING THE COMPLEX
PROTEIN UNFOLDING LANDSCAPE
Alastair Smith
Department of Physics and Astronomy
and
Astbury Centre for Structural Molecular Biology, University of Leeds, UK
The effect of applied force on the energy landscape that describes protein
conformation is an exciting and challenging topic in molecular biophysics.
Recently it has become possible to use nanotechnology tools such as the atomic
force microscope and laser tweezers to manipulate individual molecules and
explore the complex free energy landscape that describes protein conformation.
The method of mechanically unfolding single proteins using the atomic force
microscope has been applied to a handful of naturally occurring and synthetic
hetero- and homo-polyproteins. However, until now it has only been possible to
unfold a protein by pulling on the two ends of the molecule, and this only allows a
single pathway through the energy landscape to be explored. Here, experimental
data and molecular dynamics simulations of the unfolding of a single protein due
to force applied in two different directions will be presented and discussed. These
measurements open the way for a detailed exploration of the energy landscape and
a thorough comparison between experiment and theory.