Kinetics and Energetics of Biomolecular Folding and Binding

Christopher Pierse
Department of Physics
UC San Diego


Abstract: The ability of biomolecules to fold and to bind to other molecules is fundamental to virtually every living process. Advanced experimental techniques can now reveal how single biomolecules fold or bind against mechanical force, with the force serving as both the regulator and the probe of folding and binding transitions. Here, we present analytical expressions suitable for fitting the major experimental output - the distribution of folding or binding forces - from such experiments to enable their analysis and interpretation. The developed theory accounts for the compliance of the unfolded state, as well as for the effect of the tether used to co-localize the ligand and receptor in single-molecule binding experiments. A fit to the derived analytical expressions yields the key determinants of the folding and binding processes: the intrinsic on-rate and the location and height of the activation barrier. The analytical expressions are applicable to a broad range of biomolecular transitions, from the folding of nucleic acids and proteins to the binding of ligand-receptor complexes.