Stretching biomolecules

RNA & Protein folding

Molecular Motors

Single molecule force spectroscopy

Deciphering the energy landscape of biomolecules

Polymer Physics


Deciphering the energy landscape of biomolecules

Hidden Complexity in the Isomerization Dynamics of Holliday Junctions (Nature Chem. '13)

A plausible consequence of the rugged folding energy landscapes inherent to biomolecules is that there may be more than one functionally competent folded state. Indeed, molecule-to-molecule variations in the folding dynamics of enzymes and ribozymes have recently been identified in single-molecule experiments, but without systematic quantification or an understanding of their structural origin. Here, using concepts from glass physics and complementary clustering analysis, we provide a quantitative method to analyse single-molecule fluorescence resonance energy transfer (smFRET) data, thereby probing the isomerization dynamics of Holliday junctions, which display such heterogeneous dynamics over a long observation time (Tobs ≈ 40 s). We show that the ergodicity of Holliday junction dynamics is effectively broken and that their conformational space is partitioned into a folding network of kinetically disconnected clusters. Theory suggests that the persistent heterogeneity of Holliday junction dynamics is a consequence of internal multiloops with varying sizes and flexibilities frozen by Mg2+ ions. An annealing experiment using Mg2+ pulses lends support to this idea by explicitly showing that interconversions between trajectories with different patterns can be induced.

Can energy landscape roughness of proteins and RNA be measured by using mechanical unfolding experiments? (PNAS '03)

By considering temperature effects on the mechanical unfolding rates of proteins and RNA, whose energy landscape is rugged, the question posed in the title is answered in the affirmative. Adopting a theory by Zwanzig [Zwanzig, R. (1988) Proc. Natl. Acad. Sci. USA 85, 2029-2030], we show that, because of roughness characterized by an energy scale {epsilon}, the unfolding rate at constant force is retarded. Similarly, in nonequilibrium experiments  done at constant loading rates, the most probable unfolding force increases because of energy landscape roughness. The effects are dramatic at low temperatures. Our analysis suggests that, by using temperature as a variable in mechanical unfolding experiments of proteins and RNA, the ruggedness energy scale {epsilon}, can be directly measured.

Contact Information : Changbong Hyeon, Professor, School of Computational Sciences, Korea Institute for Advanced Study , Seoul 02455, Republic of Korea
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