Stretching biomolecules

RNA & Protein folding

Molecular Motors

Single molecule force spectroscopy

Deciphering the energy landscape of biomolecules

Polymer Physics


RNA & Protein Folding

RNA and Protein Folding: Common Themes and Variations (Biochemistry '05)

Visualizing the navigation of an ensemble of unfolded molecules through the bumpy energy landscape in search of the native state gives a pictorial view of biomolecular folding. This picture, when combined with concepts in polymer theory, provides a unified theory of RNA and protein folding. Just as for proteins, the major folding free energy barrier for RNA scales sublinearly with the number of nucleotides, which allows us to extract the elusive prefactor for RNA folding. Several folding scenarios can be anticipated by considering variations in the energy landscape that depend on sequence, native topology, and external conditions. RNA and protein folding mechanism can be described by the kinetic partitioning mechanism (KPM) according to which a fraction () of molecules reaches the native state directly, whereas the remaining fraction gets kinetically trapped in metastable conformations. For two-state folders 1. Molecular chaperones are recruited to assist protein folding whenever is small. We show that the iterative annealing mechanism, introduced to describe chaperonin-mediated folding, can be generalized to understand protein-assisted RNA folding. The major differences between the folding of proteins and RNA arise in the early stages of folding. For RNA, folding can only begin after the polyelectrolyte problem is solved, whereas protein collapse requires burial of hydrophobic residues. Cross-fertilization of ideas between the two fields should lead to an understanding of how RNA and proteins solve their folding problems.

Multiple Probes are Required to Explore and Control the Rugged Energy Landscape of RNA Hairpins (JACS  '08)

Brownian dynamics simulations, as a function of temperature (T) and force (f) show that RNA hairpins form by multiple pathways thus revealing the rugged nature of the free-energy landscape. While low dimensional free-energy profiles can account for some aspects of thermodynamics of hairpin formation they cannot account for the observed pathway diversity during the refolding process. Thus, a single free-energy surface cannot be used to infer the experimentally observed multistate kinetics in hairpin formation in nucleic acids. The profound differences between the kinetics of folding upon f- and T-quench is due to the slow rate of loop nucleation when the search for the native conformation commences from stretched conformations as is the case upon f-quench.

Contact Information : Changbong Hyeon, Professor, School of Computational Sciences, Korea Institute for Advanced Study , Seoul 02455, Republic of Korea
+82-2-958-3810 (tel)

© 2010 KIAS Theoretical and Computational Biophysics Group